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::Postsynaptic organizational protein complexes play central roles both in orchestrating synapse formation and in defining the functional properties of synaptic transmission that together shape the flow of information through neuronal networks. A key component of these organizational protein complexes is the family of s...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.abd8379
更新日期:2020-12-22 00:00:00
abstract::The prevalence, presentation, and progression of Alzheimer's disease (AD) differ between men and women, although β-amyloid (Aβ) deposition is a pathological hallmark of AD in both sexes. Aβ-induced activation of the neuronal glutamate receptor mGluR5 is linked to AD progression. However, we found that mGluR5 exhibits ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.abd2494
更新日期:2020-12-15 00:00:00
abstract::Overuse of β2-adrenoceptor agonist bronchodilators evokes receptor desensitization, decreased efficacy, and an increased risk of death in asthma patients. Bronchodilators that do not target β2-adrenoceptors represent a critical unmet need for asthma management. Here, we characterize the utility of osthole, a coumarin ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aax0273
更新日期:2020-11-24 00:00:00
abstract::Precise control of the activity and abundance of ubiquitin-conjugating enzymes (E2s) ensures fidelity in ubiquitin chain synthesis. In this issue of Science Signaling, Liess et al. demonstrate that the human anaphase-promoting complex (APC/C)-associated E2 UBE2S adopts an autoinhibited dimeric state that increases the...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.abd9892
更新日期:2020-10-20 00:00:00
abstract::The reciprocal regulation of phosphoprotein phosphatases (PPPs) by protein kinases is essential to cell cycle progression and control, particularly during mitosis for which the role of kinases has been extensively studied. PPPs perform much of the serine/threonine dephosphorylation in eukaryotic cells and achieve subs...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aba7823
更新日期:2020-09-08 00:00:00
abstract::The oral bacterium Fusobacterium nucleatum is often found in colorectal cancer (CRC). In the 21 July 2020 issue of Science Signaling, Casasanta et al show that CRC cell-resident F. nucleatum promotes cytokine secretion that may potentiate tumor growth and metastatic progression in patients. ...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.abc4218
更新日期:2020-08-11 00:00:00
abstract::Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a central role in Ca2+ signaling throughout the body. In the hippocampus, CaMKII is required for learning and memory. Vertebrate genomes encode four CaMKII homologs: CaMKIIα, CaMKIIβ, CaMKIIγ, and CaMKIIδ. All CaMKIIs consist of a kinase domain, a regulator...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aaz0240
更新日期:2020-07-21 00:00:00
abstract::TRPML1 (transient receptor potential mucolipin 1) is a Ca2+-permeable, nonselective cation channel localized to the membranes of endosomes and lysosomes and is not present or functional on the plasma membrane. Ca2+ released from endosomes and lysosomes into the cytosol through TRPML1 channels is vital for trafficking,...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aba1015
更新日期:2020-06-23 00:00:00
abstract::Clinical response to chimeric antigen receptor (CAR) T cell therapy is correlated with CAR T cell persistence, especially for CAR T cells that target CD19+ hematologic malignancies. 4-1BB-costimulated CAR (BBζ) T cells exhibit longer persistence after adoptive transfer than do CD28-costimulated CAR (28ζ) T cells. 4-1B...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aay8248
更新日期:2020-03-31 00:00:00
abstract::New therapeutic approaches for chronic inflammatory diseases such as inflammatory bowel disease, rheumatoid arthritis, and psoriasis are needed because current treatments are often suboptimal in terms of both efficacy and the risks of serious adverse events. Inhibitor of apoptosis proteins (IAPs) are E3 ubiquitin liga...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.aax8295
更新日期:2020-02-18 00:00:00
abstract::The advent of deep-sequencing techniques has revealed that mutations in G protein-coupled receptor (GPCR) signaling pathways in cancer are more prominent than was previously appreciated. An emergent theme is that cancer-associated mutations tend to cause enhanced GPCR pathway activation to favor oncogenicity. Regulato...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aax8620
更新日期:2020-02-04 00:00:00
abstract::Acute cardiorespiratory responses to O2 deficiency are essential for physiological homeostasis. The prototypical acute O2-sensing organ is the carotid body, which contains glomus cells expressing K+ channels whose inhibition by hypoxia leads to transmitter release and activation of nerve fibers terminating in the brai...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aay9452
更新日期:2020-01-21 00:00:00
abstract::Genetic diversity in human natural killer (NK) cell receptors is linked to resistance and susceptibility to many diseases. Here, we tested the effect of this diversity on the nanoscale organization of killer cell immunoglobulin-like receptors (KIRs). Using superresolution microscopy, we found that inhibitory KIRs enco...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aaw9252
更新日期:2019-12-17 00:00:00
abstract::Deoxyhypusine synthase (DHPS) uses the polyamine spermidine to catalyze the hypusine modification of the mRNA translation factor eIF5A and promotes oncogenesis through poorly defined mechanisms. Because germline deletion of Dhps is embryonically lethal, its role in normal postnatal cellular function in vivo remains un...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aax0715
更新日期:2019-12-03 00:00:00
abstract::Dickkopf1 (DKK1) was originally identified as an antagonist of Wnt signaling that binds to and induces the clathrin-mediated endocytosis of the Wnt coreceptors low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6). DKK1 also binds to cytoskeleton-associated protein 4 (CKAP4), which was originally identifi...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aat9519
更新日期:2019-11-19 00:00:00
abstract::Transitional B cells must actively undergo selection for self-tolerance before maturing into their resting follicular B cell successors. We found that metabolic quiescence was acquired at the follicular B cell stage in both humans and mice. In follicular B cells, the expression of genes involved in ribosome biogenesis...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aaw5573
更新日期:2019-10-22 00:00:00
abstract::The K+/Cl- cotransporter KCC2 is a molecular switch between excitatory and inhibitory effects of GABAergic inputs into neurons. In a pair of exciting studies, Watanabe et al. and Pisella et al. elucidate the role of KCC2 dephosphorylation in this process and reveal its consequences for neurodevelopment and nervous sys...
journal_title:Science signaling
pub_type: 评论,杂志文章,评审
doi:10.1126/scisignal.aay8960
更新日期:2019-10-15 00:00:00
abstract::Intracellular calcium (Ca2+) signals are of prime importance for cellular function and behavior and are underpinned by a plethora of Ca2+ channels, pumps, transporters, and binding proteins that are regulated in complex ways. A series of biennial meetings, the International Meetings of the European Calcium Society (EC...
journal_title:Science signaling
pub_type:
doi:10.1126/scisignal.aaz0961
更新日期:2019-09-17 00:00:00
abstract::The differentiation of fibroblasts into a transient population of highly activated, extracellular matrix (ECM)-producing myofibroblasts at sites of tissue injury is critical for normal tissue repair. Excessive myofibroblast accumulation and persistence, often as a result of a failure to undergo apoptosis when tissue r...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aav3048
更新日期:2019-05-21 00:00:00
abstract::The role of the mitochondrial Ca2+ uniporter (MCU) in physiologic cell proliferation remains to be defined. Here, we demonstrated that the MCU was required to match mitochondrial function to metabolic demands during the cell cycle. During the G1-S transition (the cycle phase with the highest mitochondrial ATP output),...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aav1439
更新日期:2019-04-30 00:00:00
abstract::Store-operated Ca2+ entry (SOCE) channels are highly selective Ca2+ channels activated by the endoplasmic reticulum (ER) sensors STIM1 and STIM2. Their direct interaction with the pore-forming plasma membrane ORAI proteins (ORAI1, ORAI2, and ORAI3) leads to sustained Ca2+ fluxes that are critical for many cellular fun...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aav4663
更新日期:2019-04-23 00:00:00
abstract::Mineralocorticoid receptor (MR) antagonists are effective at treating heart failure. In this issue of Science Signaling, Oakley et al. provide new insight into their cardioprotective actions and highlight the importance of the opposing relationship between the MR and the related glucocorticoid receptor (GR) in the res...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.aaw8715
更新日期:2019-04-16 00:00:00
abstract::Uncontrolled expression of type I interferon (IFN-I) drives autoimmunity, necessitating the need for tight regulation. In this issue, Cao et al reveal a role for the kinase HIPK2 in the transcriptional control of IFN-I during antiviral immune responses. ...
journal_title:Science signaling
pub_type: 评论,杂志文章,评审
doi:10.1126/scisignal.aaw8549
更新日期:2019-03-19 00:00:00
abstract::The aggregation of α-synuclein (αSyn) is considered a key pathophysiological feature of certain neurodegenerative disorders, collectively termed synucleinopathies. Given that a prion-like, cell-to-cell transfer of misfolded αSyn has been recognized in the spreading of αSyn pathology in synucleinopathies, we investigat...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aau4543
更新日期:2019-03-12 00:00:00
abstract::The C-terminal guanine nucleotide exchange factor (GEF) module of Trio (TrioC) transfers signals from the Gαq/11 subfamily of heterotrimeric G proteins to the small guanosine triphosphatase (GTPase) RhoA, enabling Gαq/11-coupled G protein-coupled receptors (GPCRs) to control downstream events, such as cell motility an...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aav2449
更新日期:2019-02-19 00:00:00
abstract::l-Glutamate is the main excitatory neurotransmitter in the brain, with postsynaptic responses to its release predominantly mediated by AMPA-type glutamate receptors (AMPARs). A critical component of synaptic plasticity involves changes in the number of responding postsynaptic receptors, which are dynamically recruited...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.aar6889
更新日期:2019-01-01 00:00:00
abstract::Frizzleds (FZDs) are a group of seven transmembrane-spanning (7TM) receptors that belong to class F of the G protein-coupled receptor (GPCR) superfamily. FZDs bind WNT proteins to stimulate diverse signaling cascades involved in embryonic development, stem cell regulation, and adult tissue homeostasis. Frizzled 5 (FZD...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aar5536
更新日期:2018-12-04 00:00:00
abstract::Multiple sclerosis (MS) is a human disease that results from autoimmune T cells targeting myelin protein that is expressed within the central nervous system. In MS, the number of FoxP3-expressing regulatory T cells (Tregs) is reduced, which facilitates the activation of autoreactive T cells. Because aspirin (acetylsal...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aar8278
更新日期:2018-11-27 00:00:00
abstract::Fgr is a member of the Src family of nonreceptor tyrosine kinases, which are overexpressed and constitutively active in many human cancers. Fgr expression is restricted to myeloid hematopoietic cells and is markedly increased in a subset of bone marrow samples from patients with acute myeloid leukemia (AML). Here, we ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aat5916
更新日期:2018-10-23 00:00:00
abstract::Cancer-associated pain is debilitating. Understanding the mechanisms that cause it can inform drug development that may improve quality of life in patients. Here, we found that the reduced abundance of potassium channels called TRESK in dorsal root ganglion (DRG) neurons sensitized nociceptive sensory neurons and canc...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aao5150
更新日期:2018-10-16 00:00:00
abstract::Mutations in ERBB2, the gene encoding epidermal growth factor receptor (EGFR) family member HER2, are common in and drive the growth of "HER2-negative" (not ERBB2 amplified) tumors but are rare in "HER2-positive" (ERBB2 amplified) breast cancer. We analyzed DNA-sequencing data from HER2-positive patients and used cell...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aat9773
更新日期:2018-10-09 00:00:00
abstract::Neutrophil extracellular trap (NET) formation can generate short-term, functional anucleate cytoplasts and trigger loss of cell viability. We demonstrated that the necroptotic cell death effector mixed lineage kinase domain-like (MLKL) translocated from the cytoplasm to the plasma membrane and stimulated downstream NA...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aao1716
更新日期:2018-09-04 00:00:00
abstract::The cytokines of the transforming growth factor-β (TGF-β) family promote the growth and differentiation of multiple tissues, but the role of only the founding member, TGF-β, in regulating the immune responses has been extensively studied. TGF-β is critical to prevent the spontaneous activation of self-reactive T cells...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aar2125
更新日期:2018-08-28 00:00:00
abstract::Chimeric antigen receptors (CARs) link an antigen recognition domain to intracellular signaling domains to redirect T cell specificity and function. T cells expressing CARs with CD28/CD3ζ or 4-1BB/CD3ζ signaling domains are effective at treating refractory B cell malignancies but exhibit differences in effector functi...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aat6753
更新日期:2018-08-21 00:00:00
abstract::Toll-like receptor (TLR) signaling regulates macrophage activation and effector cytokine propagation in the constrained environment of a tissue. In macrophage populations, TLR4 stimulates the dose-dependent transcription of nuclear factor κB (NF-κB) target genes. However, using single-RNA counting, we found that indiv...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aaf3998
更新日期:2018-07-24 00:00:00
abstract::The activation of T cells requires the guanine nucleotide exchange factor VAV1. Using mice in which a tag for affinity purification was attached to endogenous VAV1 molecules, we analyzed by quantitative mass spectrometry the signaling complex that assembles around activated VAV1. Fifty VAV1-binding partners were ident...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aar3083
更新日期:2018-07-10 00:00:00
abstract::Although multiple steroid ligands of the glucocorticoid, mineralocorticoid, and progestin families bind to and regulate the activity of mineralocorticoid receptors (MRs), the responses to these ligands differ across species. To understand how the different domains of MRs contribute to the ligand-induced activation or ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aao1520
更新日期:2018-07-03 00:00:00
abstract::Epithelial cell polarity is linked to the control of tissue growth and tumorigenesis. The tumor suppressor and cell polarity protein lethal-2-giant larvae (Lgl) promotes Hippo signaling and inhibits Notch signaling to restrict tissue growth in Drosophila melanogaster Notch signaling is greater in lgl mutant tissue tha...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aar1976
更新日期:2018-06-05 00:00:00
abstract::Obesity or a high-fat diet represses the endoribonuclease activity of inositol-requiring enzyme 1α (IRE1α), a transducer of the unfolded protein response (UPR) in cells under endoplasmic reticulum (ER) stress. An impaired UPR is associated with hepatic steatosis and nonalcoholic fatty liver disease (NAFLD), which is c...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aao4617
更新日期:2018-05-15 00:00:00
abstract::Biophysical methods and x-ray crystallography have revealed that class A G protein-coupled receptors (GPCRs) can form homodimers. We combined computational approaches with receptor cross-linking, energy transfer, and a newly developed functional export assay to characterize the residues involved in the dimerization in...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aal2869
更新日期:2018-05-08 00:00:00