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::Fluoxetine (Prozac) is an antidepressant that is thought to act by blocking presynaptic reuptake of the neurotransmitter serotonin. Despite widespread clinical use of fluoxetine, direct evidence for this mechanism has been difficult to obtain in vivo. We have determined that fluoxetine has an additional neuromuscular ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80362-7
更新日期:1999-08-01 00:00:00
abstract::Alternative mRNA splicing of the fibronectin EDI exon is controlled by a purine-rich exonic splicing enhancer (ESE), postulated as a binding site for SR proteins. By using a transient expression alternative splicing assay combined with promoter swapping, we have demonstrated that the promoter can also control EDI spli...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80372-x
更新日期:1999-08-01 00:00:00
abstract::SNAP proteins play an essential role in membrane trafficking in eukaryotic cells. They activate and recycle SNARE proteins by serving as adaptors between SNAREs and the cytosolic chaperone NSF. We have determined the crystal structure of Sec17, the yeast homolog of alpha-SNAP, to 2.9 A resolution. Sec17 is composed of...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80190-2
更新日期:1999-07-01 00:00:00
abstract::The recruitment of the TATA box-binding protein (TBP) to promoters in vivo is often rate limiting in gene expression. We present evidence that TBP negatively autoregulates its accessibility to promoter DNA in yeast through dimerization. The crystal structure of TBP dimers was used to design point mutations in the dime...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(01)80004-6
更新日期:1999-06-01 00:00:00
abstract::The crystal structure of the autoinhibited form of Hck has been determined at 2.0 A resolution, in complex with a specific pyrazolo pyrimidine-type inhibitor, PP1. The activation segment, a key regulatory component of the catalytic domain, is unphosphorylated and is visualized in its entirety. Tyr-416, the site of act...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80357-3
更新日期:1999-05-01 00:00:00
abstract::Initiation sites for DNA synthesis in the chromosomal autonomously replicating sequence (ARS)1 of Saccharomyces cerevisiae were detected at the nucleotide level. The transition from discontinuous to continuous synthesis defines the origin of bidirectional replication (OBR), which mapped adjacent to the origin recognit...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80475-x
更新日期:1999-04-01 00:00:00
abstract::We demonstrate that the major in vivo targets of brefeldin A (BFA) in the secretory pathway of budding yeast are the three members of the Sec7 domain family of ARF exchange factors: Gea1p and Gea2p (functionally interchangeable) and Sec7p. Specific residues within the Sec7 domain are important for BFA inhibition of AR...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80455-4
更新日期:1999-03-01 00:00:00
abstract::We have used EM visualization of active genes on plasmid vectors in Xenopus oocyte nuclei to investigate the relationship between poly(A) signals and RNA polymerase II transcription termination. Although a functional poly(A) signal is required for efficient termination, cotranscriptional RNA cleavage at the poly(A) si...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80465-7
更新日期:1999-03-01 00:00:00
abstract::Various experiments have demonstrated a collaborative action of Myc and Ras, both in normal cell growth control as well as during oncogenesis. We now show that Ras enhances the accumulation of Myc activity by stabilizing the Myc protein. Whereas Myc has a very short half-life when produced in the absence of mitogenic ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80308-1
更新日期:1999-02-01 00:00:00
abstract::The pre-mRNA 5' splice site is recognized by the ACAGA box of U6 spliceosomal RNA prior to catalysis of splicing. We previously identified a mutant U4 spliceosomal RNA, U4-cs1, that masks the ACAGA box in the U4/U6 complex, thus conferring a cold-sensitive splicing phenotype in vivo. Here, we show that U4-cs1 blocks i...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80175-6
更新日期:1999-01-01 00:00:00
abstract::B and T cell receptor gene assembly by V(D)J recombination is tightly regulated during lymphoid development. The mechanisms involved in this regulation are poorly understood. Here we show that nucleosomal DNA is refractory to V(D)J cleavage. However, the presence of HMG1, a chromatin-associated nonhistone DNA-binding ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80297-x
更新日期:1998-12-01 00:00:00
abstract::In Drosophila, specification of embryonic terminal cells is controlled by the Torso receptor tyrosine kinase. Here, we analyze the molecular basis of positive (Y630) and negative (Y918) phosphotyrosine (pY) signaling sites on Torso. We find that the Drosophila homolog of RasGAP associates with pY918 and is a negative ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80287-7
更新日期:1998-12-01 00:00:00
abstract::We obtained a recessive insertion mutation in the gene encoding yeast TBP-associated factor yTAFII61/68 that impairs Gcn4p-independent and Gcn4p-activated HIS3 transcription. This mutation also reduces transcription of seven other class II genes, thus indicating a broad role for this yTAFII in RNA polymerase II transc...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80166-5
更新日期:1998-11-01 00:00:00
abstract::The S. cerevisiae SCFCdc4p ubiquitin-protein ligase complex promotes cell cycle transitions through degradation of cell cycle regulators. To investigate SCFCdc4p regulation in vivo, we examined the stability of individual SCFCdc4p components. Whereas Cdc53p and Skp1p were stable, Cdc4p, the F box-containing component ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80156-2
更新日期:1998-11-01 00:00:00
abstract::A basis for understanding specificity of molecular recognition between phosphorelay proteins has been deduced from the 2.6 A structure of the Spo0B phosphotransferase of the phosphorelay regulating sporulation initiation. Spo0B consists of two domains: an N-terminal alpha-helical hairpin domain and a C-terminal alpha/...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80148-3
更新日期:1998-10-01 00:00:00
abstract::BRCA1 and BRCA2 account for most cases of familial, early onset breast and/or ovarian cancer and encode products that each interact with hRAD51. Results presented here show that BRCA1 and BRCA2 coexist in a biochemical complex and colocalize in subnuclear foci in somatic cells and on the axial elements of developing s...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80276-2
更新日期:1998-09-01 00:00:00
abstract::Activation of NF-kappaB is achieved by ubiquitination and proteasome-mediated degradation of IkappaBalpha. We have detected modified IkappaBalpha, conjugated to the small ubiquitin-like protein SUMO-1, which is resistant to signal-induced degradation. In the presence of an E1 SUMO-1-activating enzyme, Ubch9 conjugated...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80133-1
更新日期:1998-08-01 00:00:00
abstract::Two cyclin-dependent kinases have been identified in yeast and mammalian RNA polymerase II transcription initiation complexes. We find that the two yeast kinases are indistinguishable in their ability to phosphorylate the RNA polymerase II CTD, and yet in living cells one kinase is a positive regulator and the other a...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80112-4
更新日期:1998-07-01 00:00:00
abstract::Communication between the 5' cap structure and 3' poly(A) tail of eukaryotic mRNA results in the synergistic enhancement of translation. The cap and poly(A) tail binding proteins, eIF4E and Pab1p, mediate this effect in the yeast S. cerevisiae through their interactions with different parts of the translation factor e...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80122-7
更新日期:1998-07-01 00:00:00
abstract::MRE11 and RAD50 are known to be required for nonhomologous joining of DNA ends in vivo. We have investigated the enzymatic activities of the purified proteins and found that Mre11 by itself has 3' to 5' exonuclease activity that is increased when Mre11 is in a complex with Rad50. Mre11 also exhibits endonuclease activ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80097-0
更新日期:1998-06-01 00:00:00
abstract::The hairpin ribozyme is a self-cleaving motif found in the negatives strand of the satellite RNA of some plant viruses. In its natural context, the ribozyme comprises four helices, two of which contain conserved formally unpaired loops, that are adjacent arms of a four-way RNA junction. We show that the arms that woul...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80086-6
更新日期:1998-05-01 00:00:00
abstract::The transcriptional activity of NF-kappa B is stimulated upon phosphorylation of its p65 subunit on serine 276 by protein kinase A (PKA). The transcriptional coactivator CPB/p300 associates with NF-kappa B p65 through two sites, an N-terminal domain that interacts with the C-terminal region of unphosphorylated p65, an...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80066-0
更新日期:1998-04-01 00:00:00
abstract::Serine/arginine (SR)-rich splicing factors contain an RNA binding domain and an arginine/serine (RS)-rich domain required for protein-protein interactions. In addition to their roles in the basic splicing reaction, SR proteins function as components of splicing enhancer complexes. Here, we investigate the role of RS d...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80076-3
更新日期:1998-04-01 00:00:00
abstract::HIV-1 Vpu interacts with CD4 in the endoplasmic reticulum and triggers CD4 degradation, presumably by proteasomes. Human beta TrCP identified by interaction with Vpu connects CD4 to this proteolytic machinery, and CD4-Vpu-beta TrCP ternary complexes have been detected by coimmunoprecipitation. beta TrCP binding to Vpu...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80056-8
更新日期:1998-03-01 00:00:00
abstract::In eukaryotes, tRNAs are synthesized in the nucleus and after several maturation steps exported to the cytoplasm. Here, we identify exportin-t as a specific mediator of tRNA export. It is a RanGTP-binding, importin beta-related factor with predominantly nuclear localization. It shuttles rapidly between nucleus and cyt...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80036-2
更新日期:1998-02-01 00:00:00
abstract::The Cdc28p cyclin-dependent kinase is thought to both catalyze the onset of DNA replication and prevent rereplication by blocking the reassembly of initiation complexes at replication origins. Budding yeast with mutations in the CDC16 gene represent an exception to this model, because they rereplicate DNA despite bein...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80046-5
更新日期:1998-02-01 00:00:00
abstract::Two yeast enzymes that catalyze aminoacylation of tRNAs, MetRS and GluRS, form a complex with the protein Arc1p. We show here that association of Arc1p with MetRS and GluRS is required in vivo for effective recruitment of the corresponding cognate tRNAs within this complex. Arc1p is linked to MetRS and GluRS through i...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80024-6
更新日期:1998-01-01 00:00:00
abstract::Mammalian cells constantly monitor and respond to a myriad of extracellular signals, often by using cell surface receptors. Two important classes of cell surface receptors include the receptor tyrosine kinases, which recognize peptide growth factors such as insulin, and the integrins, which most often mediate binding ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80004-0
更新日期:1997-12-01 00:00:00
abstract::We have used gene competition to distinguish between possible mechanisms of transcriptional activation of the genes of the human beta-globin locus. The insertion of a second beta-globin gene at different points in the locus shows that the more proximal beta gene competes more effectively for activation by the locus co...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80014-3
更新日期:1997-12-01 00:00:00