全文获取类型
收费全文 | 8266篇 |
免费 | 709篇 |
国内免费 | 3篇 |
出版年
2023年 | 29篇 |
2022年 | 69篇 |
2021年 | 108篇 |
2020年 | 69篇 |
2019年 | 75篇 |
2018年 | 112篇 |
2017年 | 103篇 |
2016年 | 181篇 |
2015年 | 319篇 |
2014年 | 367篇 |
2013年 | 444篇 |
2012年 | 565篇 |
2011年 | 564篇 |
2010年 | 416篇 |
2009年 | 357篇 |
2008年 | 500篇 |
2007年 | 505篇 |
2006年 | 460篇 |
2005年 | 482篇 |
2004年 | 506篇 |
2003年 | 445篇 |
2002年 | 477篇 |
2001年 | 70篇 |
2000年 | 56篇 |
1999年 | 116篇 |
1998年 | 139篇 |
1997年 | 56篇 |
1996年 | 79篇 |
1995年 | 64篇 |
1994年 | 73篇 |
1993年 | 85篇 |
1992年 | 79篇 |
1991年 | 61篇 |
1990年 | 74篇 |
1989年 | 47篇 |
1988年 | 61篇 |
1987年 | 59篇 |
1986年 | 55篇 |
1985年 | 49篇 |
1984年 | 69篇 |
1983年 | 48篇 |
1982年 | 65篇 |
1981年 | 73篇 |
1980年 | 46篇 |
1979年 | 46篇 |
1978年 | 40篇 |
1977年 | 43篇 |
1976年 | 35篇 |
1975年 | 25篇 |
1974年 | 27篇 |
排序方式: 共有8978条查询结果,搜索用时 304 毫秒
951.
Fuquan Zhang Alice Moon Kay Childs Stephen Goodbourn Linda K. Dixon 《Journal of virology》2010,84(20):10681-10689
952.
Shruthi S. Vembar Martin C. Jonikas Linda M. Hendershot Jonathan S. Weissman Jeffrey L. Brodsky 《The Journal of biological chemistry》2010,285(29):22484-22494
Hsp70 chaperones can potentially interact with one of several J domain-containing Hsp40 co-chaperones to regulate distinct cellular processes. However, features within Hsp70s that determine Hsp40 specificity are undefined. To investigate this question, we introduced mutations into the ER-lumenal Hsp70, BiP/Kar2p, and found that an R217A substitution in the J domain-interacting surface of BiP compromised the physical and functional interaction with Sec63p, an Hsp40 required for ER translocation. In contrast, interaction with Jem1p, an Hsp40 required for ER-associated degradation, was unaffected. Moreover, yeast expressing R217A BiP exhibited defects in translocation but not in ER-associated degradation. Finally, the genetic interactions of the R217A BiP mutant were found to correlate with those of known translocation mutants. Together, our results indicate that residues within the Hsp70 J domain-interacting surface help confer Hsp40 specificity, in turn influencing distinct chaperone-mediated cellular activities. 相似文献
953.
954.
Ali Morsi El-Kadi Virginie Bros-Facer Wenhan Deng Amelia Philpott Eleanor Stoddart Gareth Banks Graham S. Jackson Elizabeth M. C. Fisher Michael R. Duchen Linda Greensmith Anthony L. Moore Majid Hafezparast 《The Journal of biological chemistry》2010,285(24):18627-18639
Amyotrophic lateral sclerosis (ALS) is a debilitating and fatal late-onset neurodegenerative disease. Familial cases of ALS (FALS) constitute ∼10% of all ALS cases, and mutant superoxide dismutase 1 (SOD1) is found in 15–20% of FALS. SOD1 mutations confer a toxic gain of unknown function to the protein that specifically targets the motor neurons in the cortex and the spinal cord. We have previously shown that the autosomal dominant Legs at odd angles (Loa) mutation in cytoplasmic dynein heavy chain (Dync1h1) delays disease onset and extends the life span of transgenic mice harboring human mutant SOD1G93A. In this study we provide evidence that despite the lack of direct interactions between mutant SOD1 and either mutant or wild-type cytoplasmic dynein, the Loa mutation confers significant reductions in the amount of mutant SOD1 protein in the mitochondrial matrix. Moreover, we show that the Loa mutation ameliorates defects in mitochondrial respiration and membrane potential observed in SOD1G93A motor neuron mitochondria. These data suggest that the Loa mutation reduces the vulnerability of mitochondria to the toxic effects of mutant SOD1, leading to improved mitochondrial function in SOD1G93A motor neurons. 相似文献
955.
T. Verne Lee Linda J. Johnson Richard D. Johnson Albert Koulman Geoffrey A. Lane J. Shaun Lott Vickery L. Arcus 《The Journal of biological chemistry》2010,285(4):2415-2427
Nonribosomal peptide synthetases (NRPSs) are large, multidomain proteins that are involved in the biosynthesis of an array of secondary metabolites. We report the structure of the third adenylation domain from the siderophore-synthesizing NRPS, SidN, from the endophytic fungus Neotyphodium lolii. This is the first structure of a eukaryotic NRPS domain, and it reveals a large binding pocket required to accommodate the unusual amino acid substrate, Nδ-cis-anhydromevalonyl-Nδ-hydroxy-l-ornithine (cis-AMHO). The specific activation of cis-AMHO was confirmed biochemically, and an AMHO moiety was unambiguously identified as a component of the fungal siderophore using mass spectroscopy. The protein structure shows that the substrate binding pocket is defined by 17 amino acid residues, in contrast to both prokaryotic adenylation domains and to previous predictions based on modeling. Existing substrate prediction methods for NRPS adenylation domains fail for domains from eukaryotes due to the divergence of their signature sequences from those of prokaryotes. Thus, this new structure will provide a basis for improving prediction methods for eukaryotic NRPS enzymes that play important and diverse roles in the biology of fungi. 相似文献
956.
957.
958.
959.
Jerry F. Tien Neil T. Umbreit Daniel R. Gestaut Andrew D. Franck Jeremy Cooper Linda Wordeman Tamir Gonen Charles L. Asbury Trisha N. Davis 《The Journal of cell biology》2010,189(4):713-723
The coupling of kinetochores to dynamic spindle microtubules is crucial for chromosome positioning and segregation, error correction, and cell cycle progression. How these fundamental attachments are made and persist under tensile forces from the spindle remain important questions. As microtubule-binding elements, the budding yeast Ndc80 and Dam1 kinetochore complexes are essential and not redundant, but their distinct contributions are unknown. In this study, we show that the Dam1 complex is a processivity factor for the Ndc80 complex, enhancing the ability of the Ndc80 complex to form load-bearing attachments to and track with dynamic microtubule tips in vitro. Moreover, the interaction between the Ndc80 and Dam1 complexes is abolished when the Dam1 complex is phosphorylated by the yeast aurora B kinase Ipl1. This provides evidence for a mechanism by which aurora B resets aberrant kinetochore–microtubule attachments. We propose that the action of the Dam1 complex as a processivity factor in kinetochore–microtubule attachment is regulated by conserved signals for error correction. 相似文献
960.
Robert F. Gonzalez Lennell Allen Linda Gonzales Philip L. Ballard Leland G. Dobbs 《The journal of histochemistry and cytochemistry》2010,58(10):891-901
The pulmonary alveolar epithelium is composed of two morphologically distinct cell types, type I (TI) and type II (TII) cells. Alveolar TII cells synthesize, secrete, and recycle surfactant components; contain ion transporters; and secrete immune effector molecules. In response to alveolar injury, TII cells have the capacity to act as progenitor cells, proliferating and transdifferentiating into TI cells. Although various proteins are associated with TII cells, a plasma membrane marker specific to human TII cells that would be useful for identification in tissue and for isolating this cell type has not been described previously. We devised a strategy to produce a monoclonal antibody (MAb) specific to the apical surface of human TII cells and developed an MAb that appears to be specific for human TII cells. The antibody recognizes a 280- to 300-kDa protein, HTII-280, which has the biochemical characteristics of an integral membrane protein. HTII-280 is detected by week 11 of gestation and is developmentally regulated. HTII-280 is useful for isolating human TII cells with purities and viabilities >95%. HTII-280 is likely to be a useful morphological and biochemical marker of human TII cells that may help to advance our understanding of various lung pathological conditions, including the origin and development of various lung tumors. (J Histochem Cytochem 58:891–901, 2010) 相似文献