全文获取类型
收费全文 | 5808篇 |
免费 | 600篇 |
国内免费 | 3篇 |
专业分类
6411篇 |
出版年
2022年 | 43篇 |
2021年 | 91篇 |
2020年 | 55篇 |
2019年 | 72篇 |
2018年 | 81篇 |
2017年 | 73篇 |
2016年 | 138篇 |
2015年 | 212篇 |
2014年 | 228篇 |
2013年 | 297篇 |
2012年 | 317篇 |
2011年 | 378篇 |
2010年 | 229篇 |
2009年 | 238篇 |
2008年 | 265篇 |
2007年 | 307篇 |
2006年 | 218篇 |
2005年 | 256篇 |
2004年 | 253篇 |
2003年 | 267篇 |
2002年 | 248篇 |
2001年 | 111篇 |
2000年 | 113篇 |
1999年 | 94篇 |
1998年 | 75篇 |
1997年 | 55篇 |
1996年 | 67篇 |
1995年 | 51篇 |
1994年 | 62篇 |
1993年 | 57篇 |
1992年 | 72篇 |
1991年 | 71篇 |
1990年 | 71篇 |
1989年 | 68篇 |
1988年 | 68篇 |
1987年 | 53篇 |
1986年 | 45篇 |
1985年 | 51篇 |
1984年 | 55篇 |
1983年 | 54篇 |
1982年 | 45篇 |
1981年 | 66篇 |
1980年 | 41篇 |
1979年 | 48篇 |
1978年 | 46篇 |
1977年 | 49篇 |
1976年 | 41篇 |
1975年 | 36篇 |
1974年 | 56篇 |
1973年 | 36篇 |
排序方式: 共有6411条查询结果,搜索用时 15 毫秒
131.
VanLoock MS Agrawal RK Gabashvili IS Qi L Frank J Harvey SC 《Journal of molecular biology》2000,304(4):507-515
The ribosome undergoes pronounced periodic conformational changes during protein synthesis. Of particular importance are those occurring around the decoding site, the region of the 16 S rRNA interacting with the mRNA-(tRNA)(2) complex. We have incorporated structural information from X-ray crystallography and nuclear magnetic resonance into cryo-electron microscopic maps of ribosomal complexes designed to capture structural changes at the translocation step of the polypeptide elongation cycle. The A-site region of the decoding site actively participates in the translocation of the tRNA from the A to the P-site upon GTP hydrolysis by elongation factor G, shifting approximately 8 A toward the P-site. This implies that elongation factor G actively pushes both the decoding site and the mRNA/tRNA complex during translocation. 相似文献
132.
133.
Insulation and wiring specificity of BceR‐like response regulators and their target promoters in Bacillus subtilis 下载免费PDF全文
Chong Fang Anna Nagy‐Staroń Martin Grafe Ralf Heermann Kirsten Jung Susanne Gebhard Thorsten Mascher 《Molecular microbiology》2017,104(1):16-31
BceRS and PsdRS are paralogous two‐component systems in Bacillus subtilis controlling the response to antimicrobial peptides. In the presence of extracellular bacitracin and nisin, respectively, the two response regulators (RRs) bind their target promoters, PbceA or PpsdA, resulting in a strong up‐regulation of target gene expression and ultimately antibiotic resistance. Despite high sequence similarity between the RRs BceR and PsdR and their known binding sites, no cross‐regulation has been observed between them. We therefore investigated the specificity determinants of PbceA and PpsdA that ensure the insulation of these two paralogous pathways at the RR–promoter interface. In vivo and in vitro analyses demonstrate that the regulatory regions within these two promoters contain three important elements: in addition to the known (main) binding site, we identified a linker region and a secondary binding site that are crucial for functionality. Initial binding to the high‐affinity, low‐specificity main binding site is a prerequisite for the subsequent highly specific binding of a second RR dimer to the low‐affinity secondary binding site. In addition to this hierarchical cooperative binding, discrimination requires a competition of the two RRs for their respective binding site mediated by only slight differences in binding affinities. 相似文献
134.
Jan Klein Christophe Benoist Chella S. David Peter Demant Kirsten Fischer Lindahl Lorraine Flaherty Richard A. Flavell Ulrich Hämmerling Leroy E. Hood Stephen W. Hunt III Patricia P. Jones Philippe Kourilsky Hugh O. McDevitt Daniel Meruelo Donal B. Murphy Stanley G. Nathenson David H. Sachs Michael Steinmetz Susumu Tonegawa Edward K. Wakeland Elizabeth H. Weiss 《Immunogenetics》1990,32(3):147-149
135.
The complete primary structure of the human snRNP E protein. 总被引:4,自引:2,他引:4
D R Stanford M Kehl C A Perry E L Holicky S E Harvey A M Rohleder K Rehder Jr R Luhrmann E D Wieben 《Nucleic acids research》1988,16(22):10593-10605
The snRNP E protein is one of four "core" proteins associated with the snRNAs of the U family (U1,U2,U4,U5, and U6). Screening of a human teratoma cDNA library with a partial cDNA for a human autoimmune antigen resulted in the isolation of a cDNA clone containing the entire coding region of this snRNP core protein. Comparison of the 5' end of this cDNA with the sequences of two processed pseudogenes and primer extension data suggest that the cDNA is nearly full length. The longest open reading frame in this clone codes for a basic 92 amino acid protein which is in perfect agreement with amino acid sequence data obtained from purified E protein. The predicted sequence of this protein reveals no extensive similarity to other snRNP proteins, but contains regions of similarity to a eukaryotic ribosomal protein. 相似文献
136.
137.
138.
Phospholipid lamellae are cholesterol carriers in human bile 总被引:2,自引:0,他引:2
G J S?mjen Y Marikovsky E Wachtel P R Harvey R Rosenberg S M Strasberg T Gilat 《Biochimica et biophysica acta》1990,1042(1):28-35
Cholesterol solubility and precipitation in bile are major factors in the pathogenesis of cholesterol gallstones. At present, mixed micelles and phospholipid vesicles are considered to be the only cholesterol carriers in bile. In this study we present evidence showing that phospholipid lamellae are major cholesterol carriers in human bile. Lamellae are a known aggregational form in pure phospholipid model systems. In the present study, lamellae were demonstrated by electron microscopy after negative staining and by small-angle X-ray diffraction in all human gallbladder bile samples examined. During diffraction experiments, cholesterol was found to crystallize from these lamellae. Cholesterol carriers in bile were separated by high-resolution chromatography and by prolonged ultracentrifugation. Lamellae were shown to solubilize most of the biliary cholesterol; vesicles solubilized a lesser amount; while micelles solubilized only a minor portion. Our data suggest that phospholipid aggregates are the main cholesterol carriers in bile. Bile salts may control the equilibrium between the various aggregational forms of cholesterol-carrying phospholipids. 相似文献
139.
Jäger E Salter R Castelli C Höhn H Freitag K Karbach J Neukirch C Necker A Knuth A Maeurer MJ 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(6):2766-2772
Soluble MHC class I molecules loaded with antigenic peptides are available either to detect and to enumerate or, alternatively, to sort and expand MHC class I-restricted and peptide-reactive T cells. A defined number of MHC class I/peptide complexes can now be implemented to measure T cell responses induced upon Ag-specific stimulation, including CD3/CD8/zeta-chain down-regulation, pattern, and quantity of cytokine secretion. As a paradigm, we analyzed the reactivity of a Melan-A/MART-1-specific and HLA-A2-restricted CD8(+) T cell clone to either soluble or solid-phase presented peptides, including the naturally processed and presented Melan-A/MART-1 peptide AAGIGILTV or the peptide analog ELAGIGILTV presented either by the HLA-A2 wild-type (wt) or mutant (alanineright arrowvaline aa 245) MHC class I molecule, which reduces engagement of the CD8 molecule with the HLA-A2 heavy chain. Soluble MHC class I complexes were used as either monomeric or tetrameric complexes. Soluble monomeric MHC class I complexes, loaded with the Melan-A/MART-1 peptide, resulted in CD3/CD8 and TCR zeta-chain down-regulation, but did not induce measurable cytokine release. In general, differences pertaining to CD3/CD8/zeta-chain regulation and cytokine release, including IL-2, IFN-gamma, and GM-CSF, were associated with 1) the format of Ag presentation (monomeric vs tetrameric MHC class I complexes), 2) wt vs mutant HLA-A2 molecules, and 3) the target Ag (wt vs analog peptide). These differences are to be considered if T cells are exposed to recombinant MHC class I Ags loaded with peptides implemented for detection, activation, or sorting of Ag-specific T cells. 相似文献
140.
Harvey J 《Molecular neurobiology》2003,28(3):245-258
It is well established that the adipocyte-derived hormone leptin is an important circulating satiety factor that regulates
body weight and food intake via its actions on specific hypothalamic nuclei. However, there is growing evidence that leptin
and its receptors are widely expressed throughout the brain, in regions not generally associated with energy homeostasis,
such as cortex, cerebellum, brainstem, basal ganglia, and hippocampus. In this review the author discusses recent advances
made in leptin neurobiology, with particular emphasis on the role of this endocrine peptide in normal and pathophysiological
hippocampal function. 相似文献