解剖学和形态学
麻醉学
听力与言语-语言病理学
行为科学
心脏和心血管系统
细胞和组织工程学
临床神经病学
危重症监护医学
牙科,口腔外科和医学
皮肤病学
急诊医学
内分泌学和新陈代谢
肠胃学和肝脏学
老人病学和老年医学
卫生保健科学和服务
血液学
免疫学
传染病
综合和补充性医学
医学伦理学
医学信息学
医学实验室技术
医学,全科和内科
医学,法律
医学,研究和试验
神经系统科学
护理
营养学和饮食学
产科医学和妇科医学
肿瘤学
眼科学
整形外科学
耳鼻喉科学
病理学
儿科学
周围血管疾病
药理学和药剂学
生理学
基本医疗保健
精神病学
公共、环境和职业卫生
放射学,核医学和医学成像
康复学
生殖生物学
呼吸系统
风湿病学
运动科学
外科学
毒理学
热带医学
泌尿学和肾脏学
病毒学
老年医学
健康政策和服务
心理学,临床
abstract::Hedgehog (Hh) signaling plays varied and critical roles in animal development, homeostasis, and disease. The core components of the canonical pathway and many key modulators of signaling have been identified, as have mechanisms by which the quantity and quality of signaling through the pathway are modulated. New resea...
journal_title:Science signaling
pub_type: 社论
doi:10.1126/scisignal.2002653
更新日期:2011-11-22 00:00:00
abstract::Progression through mitosis depends on a large number of protein complexes that regulate the major structural and physiological changes necessary for faithful chromosome segregation. Most, if not all, of the mitotic processes are regulated by a set of mitotic protein kinases that control protein activity by phosphoryl...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2001993
更新日期:2011-11-08 00:00:00
abstract::The mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 2 (ERK2) is ubiquitously expressed in mammalian tissues and is involved in a wide range of biological processes. Although MAPKs have been intensely studied, identification of their substrates remains challenging. We have optimized a chem...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2002010
更新日期:2011-10-25 00:00:00
abstract::Phosphoinositide 3-kinases (PI3Ks) are implicated in a broad spectrum of cellular activities, such as growth, proliferation, differentiation, migration, and metabolism. Activation of class I PI3Ks by mutation or overexpression correlates with the development and maintenance of various human cancers. These PI3Ks are he...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.2002165
更新日期:2011-10-18 00:00:00
abstract::Bone morphogenetic proteins (BMPs) and Wnts are growth factors that provide essential patterning signals for cell proliferation and differentiation. Here, we describe a molecular mechanism by which the phosphorylation state of the Drosophila transcription factor Mad determines its ability to transduce either BMP or Wi...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2002034
更新日期:2011-10-11 00:00:00
abstract::During T cell activation by antigen-presenting cells (APCs), the diverse spatiotemporal organization of components of T cell signaling pathways modulates the efficiency of activation. Here, we found that loss of the tyrosine kinase interleukin-2 (IL-2)-inducible T cell kinase (Itk) in mice altered the spatiotemporal d...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2001821
更新日期:2011-10-04 00:00:00
abstract::GIV (Gα-interacting vesicle-associated protein; also known as Girdin) enhances Akt activation downstream of multiple growth factor- and G protein (heterotrimeric guanosine 5'-triphosphate-binding protein)-coupled receptors to trigger cell migration and cancer invasion. We demonstrate that GIV is a tyrosine phosphoprot...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2002049
更新日期:2011-09-27 00:00:00
abstract::This two-part lecture introduces students to the scientific computing language MATLAB. Prior computer programming experience is not required. The lectures present basic concepts of computer programming logic that tend to cause difficulties for beginners in addition to concepts that relate specifically to the MATLAB la...
journal_title:Science signaling
pub_type:
doi:10.1126/scisignal.2001984
更新日期:2011-09-13 00:00:00
abstract::Inositol pyrophosphates are highly energetic inositol polyphosphate molecules present in organisms from slime molds and yeast to mammals. Distinct classes of enzymes generate different forms of inositol pyrophosphates. The biosynthesis of these substances principally involves phosphorylation of inositol hexakisphospha...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.2001958
更新日期:2011-08-23 00:00:00
abstract::Compared with the luminal subtype, the basal-like subtype of breast cancer has an aggressive clinical behavior, but the reasons for this difference between the two subtypes are poorly understood. We identified microRNAs (miRNAs) miR-221 and miR-222 (miR-221/222) as basal-like subtype-specific miRNAs that decrease expr...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2002258
更新日期:2011-08-09 00:00:00
abstract::MicroRNAs (miRNAs), key posttranscriptional regulators of many biological processes, have been implicated in many diseases, including cancer. In a recent paper, Avraham and colleagues take a systems biology approach to determine whether and how miRNAs are involved in the regulation of oncogenic signaling networks down...
journal_title:Science signaling
pub_type: 评论,杂志文章,评审
doi:10.1126/scisignal.2002182
更新日期:2011-07-26 00:00:00
abstract::Notch signaling is used to choose cell fates in many developmental contexts. New evidence shows that circulating blood cells in Drosophila, in the absence of Notch ligand provided by neighboring cells, activate Notch signaling through stabilization with the hypoxia-inducible factor-α (HIF-α) transcription factor. Alth...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.2002277
更新日期:2011-07-12 00:00:00
abstract::Adenosine 5'-diphosphate (ADP)-ribosylation is a protein posttranslational modification that is catalyzed by ADP-ribosyltransferases (ARTs), using nicotinamide adenine dinucleotide (NAD(+)) as a substrate. Mono-ribosylation can be extended into polymers of ADP-ribose (PAR). Poly(ADP-ribosyl)polymerase (PARP) 1, the be...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2001645
更新日期:2011-05-24 00:00:00
abstract::Cancer cells acquire resistance to DNA-damaging therapeutic agents, such as cisplatin, but the genetic mechanisms through which this occurs remain unclear. We show that the c-MYC oncoprotein increases cisplatin resistance by decreasing production of the c-MYC inhibitor BIN1 (bridging integrator 1). The sensitivity of ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2001556
更新日期:2011-03-29 00:00:00
abstract::Ligand binding to certain heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) stimulates the rapid synthesis of cyclic adenosine monophosphate (cAMP) through the G protein α(s) subunit, which activates adenylyl cyclase (AC). We found that the transmembrane receptor low-density lipop...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2001464
更新日期:2011-03-15 00:00:00
abstract::Regulatory T (T(reg)) cells are a unique CD4(+) T cell lineage that plays a crucial role in the maintenance of immunological tolerance. The Forkhead box transcription factor Foxp3 is critically involved in T(reg) cell development and responsible for determining the suppressive function of these cells. The majority of ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2001783
更新日期:2011-02-01 00:00:00
abstract::The proteasome plays a pivotal role in the cellular response to oxidative stress. Here, we used biochemical and mass spectrometric methods to investigate structural changes in the 26S proteasomes from yeast and mammalian cells exposed to hydrogen peroxide (H₂O₂). Oxidative stress induced the dissociation of the 20S co...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2001232
更新日期:2010-12-07 00:00:00
abstract::Microglia mediate neuroprotection and neuropathogenesis but have not been directly associated with behavior. As gatekeepers of the brain's immune system, microglia protect the brain from pathogens but also contribute to inflammation, which may negatively affect neurons. A recent study demonstrates a role for Hoxb8-exp...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.3147jc8
更新日期:2010-11-09 00:00:00
abstract::Most metazoans have at least some ability to regenerate damaged cells and tissues, although the regenerative capacity varies depending on the species, organ, or developmental stage. Cell replacement and regeneration occur in two contexts: renewal of spent cells during tissue homeostasis (homeostatic growth), and in re...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.3145re8
更新日期:2010-10-26 00:00:00
abstract::When we are frightened, our hearts beat more rapidly and forcefully so we can fight more intensely or run away faster. This fight-or-flight response is triggered by the release of norepinephrine from neurons of the sympathetic nervous system. Norepinephrine activates the classic β-adrenergic receptor-heterotrimeric G(...
journal_title:Science signaling
pub_type: 评论,杂志文章
doi:10.1126/scisignal.3141pe33
更新日期:2010-09-28 00:00:00
abstract::Chemokines were initially thought of only as regulators of the migration of developing thymocytes between different compartments of the thymus and were predicted also to be involved in early stages of thymocyte development. Recent data have suggested additional functions for the chemokine receptor CXCR4-a G protein-co...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.3119jc4
更新日期:2010-04-27 00:00:00
abstract::Phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins play essential roles in DNA-based and RNA-based processes, such as the response to DNA damage, messenger RNA (mRNA) quality control, transcription, and translation, where they contribute to the maintenance of genome integrity and accurate gene...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2000468
更新日期:2010-04-06 00:00:00
abstract::Secretory cells, such as pancreatic beta cells, face the challenge of increasing protein synthesis severalfold during acute or chronic stimulation. This poses a burden on the endoplasmic reticulum (ER), the organelle where proinsulin synthesis and folding takes place. Thus, beta cells use various adaptive mechanisms t...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.3110pe7
更新日期:2010-02-23 00:00:00
abstract::Jasmonates control defense gene expression, growth, and fertility throughout the plant kingdom and have been studied extensively in Arabidopsis thaliana. The prohormone jasmonic acid (JA) is conjugated to amino acids such as isoleucine to form the active hormone jasmonoyl-isoleucine (JA-Ile). A series of breakthroughs...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.3109cm4
更新日期:2010-02-16 00:00:00
abstract::The capacity of a rabies virus to promote neuronal survival (a signature of virulence) or death (a marker of attenuation) depends on the cellular partners recruited by the PDZ-binding site (PDZ-BS) of its envelope glycoprotein (G). Neuronal survival requires the selective association of the PDZ-BS of G with the PDZ do...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2000510
更新日期:2010-01-19 00:00:00
abstract::Like phosphorylation, the addition of O-linked beta-N-acetylglucosamine (O-GlcNAcylation) is a ubiquitous, reversible process that modifies serine and threonine residues on nuclear and cytoplasmic proteins. Overexpression of the enzyme that adds O-GlcNAc to target proteins, O-GlcNAc transferase (OGT), perturbs cytokin...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2000526
更新日期:2010-01-12 00:00:00
abstract::Nominations for this year's signaling breakthroughs spanned physiology, therapeutics and drug development, neuroscience, and plant signaling. Among the most exciting advances in mammalian biology were therapeutic applications of research that are overturning the conventional boundaries of signaling pathways,unexpected...
journal_title:Science signaling
pub_type: 社论,历史文章,评审
doi:10.1126/scisignal.3103eg1
更新日期:2010-01-05 00:00:00
abstract::Inhibition of protein synthesis by phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2) at Ser(51) occurs as a result of the activation of a family of kinases in response to various forms of stress. Although some consequences of eIF2alpha phosphorylation are cytoprotective, phospho...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2000389
更新日期:2009-12-22 00:00:00
abstract::The fluorescent properties of the amino acid tryptophan make it a useful tool for fluorometric assays. Because tryptophan fluorescence is remarkably sensitive to the polarity of the environment, it can be used to determine the affinity of tryptophan-containing peptides for phospholipid vesicles of varying compositions...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.299pl4
更新日期:2009-12-01 00:00:00
abstract::For the first 30 years since its discovery, reversible protein acetylation has been studied and understood almost exclusively in the context of histone modification and gene transcription. With the discovery of non-histone acetylated proteins and acetylation-modifying enzymes in cellular compartments outside the nucle...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.297pe76
更新日期:2009-11-17 00:00:00
abstract::For decades, the fission yeast Schizosaccharomyces pombe has been used as an excellent model with which to explore how cellular growth is coordinated with the division cycle, a yet-unanswered question in biology. New studies in this organism show that TOR (target of rapamycin) kinase and stress-responsive MAPK (mitoge...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.296pe74
更新日期:2009-11-10 00:00:00
abstract::Regulatory factor X (Rfx) homologs regulate the transcription of genes necessary for ciliogenesis in invertebrates and vertebrates. Primary cilia are necessary for Hedgehog signaling and regulation of the activity of the transcriptional regulators known as Gli proteins, which are targets of Hedgehog signaling. Here, w...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2000602
更新日期:2009-11-03 00:00:00
abstract::MKK4 (mitogen-activated protein kinase kinase 4) is a pivotal upstream activator of c-Jun N-terminal kinase and p38. Here, we report that the abundance of MKK4 increases in senescent human diploid fibroblasts through enhanced translation. We identified four microRNAs (miR-15b, miR-24, miR-25, and miR-141) that target ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2000442
更新日期:2009-10-27 00:00:00
abstract::The beta-amyloid (Abeta) peptide is associated with the pathogenesis of Alzheimer's disease (AD). Evidence gathered over the last two decades suggests that the gradual accumulation of soluble and insoluble Abeta peptide species triggers a cascade of events that leads to the clinical manifestation of AD. Abeta accumula...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.293re8
更新日期:2009-10-20 00:00:00
abstract::Morphogens form concentration gradients that organize patterns of cells and control growth. It has been suggested that, rather than the intensity of morphogen signaling, it is its gradation that is the relevant modulator of cell proliferation. According to this view, the ability of morphogens to regulate growth during...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2000360
更新日期:2009-10-06 00:00:00
abstract::Over the last 50 years, the posttranslational modification (PTM) of proteins has emerged as a central mechanism for cells to regulate metabolism, growth, differentiation, cell-cell interactions, and immune responses. By influencing protein structure and function, PTM leads to a multiplication of proteome diversity. Re...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.290re7
更新日期:2009-09-29 00:00:00
abstract::The mechanisms that determine localized formation of reactive oxygen species (ROS) through NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase (Nox) family members in nonphagocytic cells are unknown. We show that the c-Src substrate proteins Tks4 (tyrosine kinase substrate with four SH3 domains...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2000370
更新日期:2009-09-15 00:00:00
abstract::Multicellular organisms rely on complex, fine-tuned protein networks to respond to environmental changes. We used in vitro evolution to explore the role of domain mutation and expansion in the evolution of network complexity. Using random mutagenesis to facilitate family expansion, we asked how versatile and robust th...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2000416
更新日期:2009-09-08 00:00:00
abstract::The LKB1 serine-threonine kinase is a tumor suppressor that is inactivated in a large number of sporadic human lung non-small cell carcinomas (NSCLCs) and cervical cancers. Genetic deletion of LKB1 in various mouse tissues results in tumorigenesis, and loss of LKB1 increases metastasis in a mouse model of NSCLC. LKB1 ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.286pe55
更新日期:2009-09-01 00:00:00
abstract::The organization and renewal capacity of teeth vary greatly among vertebrates. Mammals have only one row of teeth that are renewed at most once, whereas many nonmammalian species have multirowed dentitions and show remarkable capacity to replace their teeth throughout life. Although knowledge on the genetic basis of t...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.285pe53
更新日期:2009-08-25 00:00:00