全文获取类型
收费全文 | 16414篇 |
免费 | 1561篇 |
国内免费 | 4篇 |
出版年
2023年 | 86篇 |
2022年 | 206篇 |
2021年 | 443篇 |
2020年 | 271篇 |
2019年 | 303篇 |
2018年 | 352篇 |
2017年 | 310篇 |
2016年 | 500篇 |
2015年 | 862篇 |
2014年 | 938篇 |
2013年 | 1024篇 |
2012年 | 1377篇 |
2011年 | 1455篇 |
2010年 | 907篇 |
2009年 | 764篇 |
2008年 | 997篇 |
2007年 | 993篇 |
2006年 | 921篇 |
2005年 | 754篇 |
2004年 | 826篇 |
2003年 | 704篇 |
2002年 | 699篇 |
2001年 | 161篇 |
2000年 | 100篇 |
1999年 | 133篇 |
1998年 | 161篇 |
1997年 | 100篇 |
1996年 | 85篇 |
1995年 | 92篇 |
1994年 | 93篇 |
1993年 | 112篇 |
1992年 | 78篇 |
1991年 | 76篇 |
1990年 | 71篇 |
1989年 | 62篇 |
1988年 | 55篇 |
1987年 | 59篇 |
1986年 | 46篇 |
1985年 | 55篇 |
1984年 | 73篇 |
1983年 | 46篇 |
1982年 | 64篇 |
1981年 | 55篇 |
1980年 | 42篇 |
1979年 | 38篇 |
1978年 | 56篇 |
1977年 | 37篇 |
1976年 | 29篇 |
1975年 | 27篇 |
1974年 | 29篇 |
排序方式: 共有10000条查询结果,搜索用时 46 毫秒
911.
Myosin VI binds to and localises with Dab2, potentially linking receptor-mediated endocytosis and the actin cytoskeleton 总被引:9,自引:3,他引:6
Morris SM Arden SD Roberts RC Kendrick-Jones J Cooper JA Luzio JP Buss F 《Traffic (Copenhagen, Denmark)》2002,3(5):331-341
Myosin VI, an actin-based motor protein, and Disabled 2 (Dab2), a molecule involved in endocytosis and cell signalling, have been found to bind together using yeast and mammalian two-hybrid screens. In polarised epithelial cells, myosin VI is known to be associated with apical clathrin-coated vesicles and is believed to move them towards the minus end of actin filaments, away from the plasma membrane and into the cell. Dab2 belongs to a group of signal transduction proteins that bind in vitro to the FXNPXY sequence found in the cytosolic tails of members of the low-density lipoprotein receptor family. The central region of Dab2, containing two DPF motifs, binds to the clathrin adaptor protein AP-2, whereas a C-terminal region contains the binding site for myosin VI. This site is conserved in Dab1, the neuronal counterpart of Dab2. The interaction between Dab2 and myosin VI was confirmed by in vitro binding assays and coimmunoprecipitation and by their colocalisation in clathrin-coated pits/vesicles concentrated at the apical domain of polarised cells. These results suggest that the myosin VI–Dab2 interaction may be one link between the actin cytoskeleton and receptors undergoing endocytosis. 相似文献
912.
An "integrated model" of programmed ribosomal frameshifting 总被引:10,自引:0,他引:10
Many viral mRNAs, including those of HIV-1, can make translating ribosomes change reading frame. Altering the efficiencies of programmed ribosomal frameshift (PRF) inhibits viral propagation. As a new target for potential antiviral agents, it is therefore important to understand how PRF is controlled. Incorporation of the current models describing PRF into the context of the translation elongation cycle leads us to propose an 'integrated model' of PRF both as a guide towards further characterization of PRF at the molecular and biochemical levels, and for the identification of new targets for antiviral therapeutics. 相似文献
913.
Without an epidermis, we would be in a sorry state. The epidermal layer not only protects us from environmental pathogens but also acts as a 'barrier' to water loss. The identification of the molecular nature of the barrier has occupied the efforts of skin researchers over many years, with the consensus in the field being that a protein-lipid layer, located in the upper layers of the epidermis, is necessary for establishment and maintenance of a water barrier. Now, evidence has been presented that components of intercellular junctions, termed tight junctions, also play an essential role in development of barrier function in the skin. Remarkably, the data support a hypothesis that was presented more than 30 years ago. 相似文献
914.
Triply mutated MATalpha2 protein, alpha2-3A, in which all three major groove-contacting residues are mutated to alanine, is defective in binding DNA alone or in complex with Mcm1 yet binds with MATa1 with near wild-type affinity and specificity. To gain insight into this unexpected behavior, we determined the crystal structure of the a1/alpha2-3A/DNA complex. The structure shows that the triple mutation causes a collapse of the alpha2-3A/DNA interface that results in a reorganized set of alpha2-3A/DNA contacts, thereby enabling the mutant protein to recognize the wild-type DNA sequence. Isothermal titration calorimetry measurements reveal that a much more favorable entropic component stabilizes the a1/alpha2-3A/DNA complex than the alpha2-3A/DNA complex. The combined structural and thermodynamic studies provide an explanation of how partner proteins influence the sequence specificity of a DNA binding protein. 相似文献
915.
Designing a 20-residue protein 总被引:6,自引:0,他引:6
Truncation and mutation of a poorly folded 39-residue peptide has produced 20-residue constructs that are >95% folded in water at physiological pH. These constructs optimize a novel fold, designated as the 'Trp-cage' motif, and are significantly more stable than any other miniprotein reported to date. Folding is cooperative and hydrophobically driven by the encapsulation of a Trp side chain in a sheath of Pro rings. As the smallest protein-like construct, Trp-cage miniproteins should provide a testing ground for both experimental studies and computational simulations of protein folding and unfolding pathways. Pro Trp interactions may be a particularly effective strategy for the a priori design of self-folding peptides. 相似文献
916.
917.
The Chediak-Higashi protein interacts with SNARE complex and signal transduction proteins 总被引:5,自引:0,他引:5
Tchernev VT Mansfield TA Giot L Kumar AM Nandabalan K Li Y Mishra VS Detter JC Rothberg JM Wallace MR Southwick FS Kingsmore SF 《Molecular medicine (Cambridge, Mass.)》2002,8(1):56-64
BACKGROUND:Chediak-Higashi syndrome (CHS) is an inherited immunodeficiency disease characterized by giant lysosomes and impaired leukocyte degranulation. CHS results from mutations in the lysosomal trafficking regulator (LYST) gene, which encodes a 425-kD cytoplasmic protein of unknown function. The goal of this study was to identify proteins that interact with LYST as a first step in understanding how LYST modulates lysosomal exocytosis. MATERIALS AND METHODS: Fourteen cDNA fragments, covering the entire coding domain of LYST, were used as baits to screen five human cDNA libraries by a yeast two-hybrid method, modified to allow screening in the activation and the binding domain, three selectable markers, and more stringent confirmation procedures. Five of the interactions were confirmed by an in vitro binding assay. RESULTS: Twenty-one proteins that interact with LYST were identified in yeast two-hybrid screens. Four interactions, confirmed directly, were with proteins important in vesicular transport and signal transduction (the SNARE-complex protein HRS, 14-3-3, and casein kinase II). CONCLUSIONS:On the basis of protein interactions, LYST appears to function as an adapter protein that may juxtapose proteins that mediate intracellular membrane fusion reactions. The pathologic manifestations observed in CHS patients and in mice with the homologous mutation beige suggest that understanding the role of LYST may be relevant to the treatment of not only CHS but also of diseases such as asthma, urticaria, and lupus, as well as to the molecular dissection of the CHS-associated cancer predisposition. 相似文献
918.
Dournon C Membre H Brohm PE Coince A Cornu N Dreyer L Florentin J Jeanneau L Henniquin C Houbre M Guerard M Lecomte N Maxant L Schluraff M Venandet AS Jusyte A Simmet D Bocking D Flaig D Santak L Bolek S Goppel V Rossignon JP Trossat MA Raux M Forster S Staudenmaier G Boser S Horn E 《Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology》2002,9(1):P375-P376
The German-French biological experiment AQUARIUS-XENOPUS which flew on the Soyuz flight Andromede to the International Space Station ISS (launched October 21, 2001 in Baikonour/Kazakhstan) was extended by an outreach project. Pupils of class 10 to 12 from Ulm/D and Nancy-Tomblaine/F studied swimming behavior of Xenopus tadpoles on ground. They were instructed to perform all experimental steps following the protocol of similar video recordings on ISS. After the flight, they evaluated the kinetics of swimming of both ground controls and space animals. The pupil project included theoretical components to introduce them to the field of gravitational biology. One feature of the project was the exchange of ideas between pupils by meetings which took place in Ulm (June 2001), Nancy (February 2002) and Paris (May 2002). We consider our approach as a successful way to include young people in space experiments on a cheap cost level and to bring ideas of gravitational biology into the curricula of European schools. 相似文献
919.
Physical mapping of genes in somatic cell radiation hybrids by comparative genomic hybridization to cDNA microarrays 总被引:1,自引:0,他引:1
Lin JY Pollack JR Chou FL Rees CA Christian AT Bedford JS Brown PO Ginsberg MH 《Genome biology》2002,3(6):research0026.1-research00267
Background
Somatic cell mutants can be informative in the analysis of a wide variety of cellular processes. The use of map-based positional cloning strategies in somatic cell hybrids to analyze genes responsible for recessive mutant phenotypes is often tedious, however, and remains a major obstacle in somatic cell genetics. To fulfill the need for more efficient gene mapping in somatic cell mutants, we have developed a new DNA microarray comparative genomic hybridization (array-CGH) method that can rapidly and efficiently map the physical location of genes complementing somatic cell mutants to a small candidate genomic region. Here we report experiments that establish the validity and efficacy of the methodology. 相似文献920.
Comprehensive gene expression analysis by transcript profiling 总被引:20,自引:0,他引:20
Donson J Fang Y Espiritu-Santo G Xing W Salazar A Miyamoto S Armendarez V Volkmuth W 《Plant molecular biology》2002,48(1-2):75-97