全文获取类型
收费全文 | 50103篇 |
免费 | 4567篇 |
国内免费 | 30篇 |
出版年
2022年 | 362篇 |
2021年 | 760篇 |
2020年 | 453篇 |
2019年 | 569篇 |
2018年 | 703篇 |
2017年 | 649篇 |
2016年 | 1043篇 |
2015年 | 1755篇 |
2014年 | 1940篇 |
2013年 | 2547篇 |
2012年 | 3225篇 |
2011年 | 3289篇 |
2010年 | 2129篇 |
2009年 | 1904篇 |
2008年 | 2716篇 |
2007年 | 2815篇 |
2006年 | 2745篇 |
2005年 | 2633篇 |
2004年 | 2531篇 |
2003年 | 2404篇 |
2002年 | 2310篇 |
2001年 | 550篇 |
2000年 | 451篇 |
1999年 | 613篇 |
1998年 | 729篇 |
1997年 | 553篇 |
1996年 | 471篇 |
1995年 | 428篇 |
1994年 | 414篇 |
1993年 | 440篇 |
1992年 | 487篇 |
1991年 | 415篇 |
1990年 | 406篇 |
1989年 | 399篇 |
1988年 | 369篇 |
1987年 | 330篇 |
1986年 | 355篇 |
1985年 | 378篇 |
1984年 | 454篇 |
1983年 | 372篇 |
1982年 | 480篇 |
1981年 | 496篇 |
1980年 | 390篇 |
1979年 | 322篇 |
1978年 | 337篇 |
1977年 | 293篇 |
1976年 | 331篇 |
1975年 | 220篇 |
1974年 | 276篇 |
1973年 | 275篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
101.
A Macintosh Hypertalk program (Hypercard stack)for use in phylogenetic comparative analysis of RNA structureis described. The program identifies covariations and compensatorychanges in RNA sequence alignments, for use in the constructionof secondary structure models or the identification of tertiaryinteractions. The results of an analysis are presented eitheras a list of positions in the alignment which covary, or asa 2-dimensional matrix in which potential helices in the secondarystructure appear as diagonal patterns.
Received on January 7, 1991; accepted on March 19, 1991 相似文献
102.
Tristan J. Iseli Nigel Turner Xiao-Yi Zeng Gregory J. Cooney Edward W. Kraegen Sheng Yao Yang Ye David E. James Ji-Ming Ye 《PloS one》2013,8(4)
We recently showed that bitter melon-derived triterpenoids (BMTs) activate AMPK and increase GLUT4 translocation to the plasma membrane in vitro, and improve glucose disposal in insulin resistant models in vivo. Here we interrogated the mechanism by which these novel compounds activate AMPK, a leading anti-diabetic drug target. BMTs did not activate AMPK directly in an allosteric manner as AMP or the Abbott compound (A-769662) does, nor did they activate AMPK by inhibiting cellular respiration like many commonly used anti-diabetic medications. BMTs increased AMPK activity in both L6 myotubes and LKB1-deficient HeLa cells by 20–35%. Incubation with the CaMKKβ inhibitor, STO-609, completely attenuated this effect suggesting a key role for CaMKKβ in this activation. Incubation of L6 myotubes with the calcium chelator EGTA-AM did not alter this activation suggesting that the BMT-dependent activation was Ca2+-independent. We therefore propose that CaMKKβ is a key upstream kinase for BMT-induced activation of AMPK. 相似文献
103.
James S. Farris Mari Källersjö 《Cladistics : the international journal of the Willi Hennig Society》1995,11(4):377-379
Abstract — Lefkovitch's formula for the probability of incompatibility between two binary characters can give incorrect results because it redundantly counts some possible compatibilities. The inaccuracy occurs when the characters have the same number of terminals showing the apomorphic state. 相似文献
104.
105.
James M. Chen Rosalyn Grad Regina Monaco Matthew R. Pincus 《Journal of Protein Chemistry》1996,15(1):11-16
rap-1A, an anti-oncogene-encoded protein, is aras-p21-like protein whose sequence is over 80% homologous to p21 and which interacts with the same intracellular target proteins and is activated by the same mechanisms as p21, e.g., by binding GTP in place of GDP. Both interact with effector proteins in the same region, involving residues 32–47. However, activated rap-1A blocks the mitogenic signal transducing effects of p21. Optimal sequence alignment of p21 and rap-1A shows two insertions of rap-1A atras positions 120 and 138. We have constructed the three-dimensional structure of rap-1A bound to GTP by using the energy-minimized three-dimensional structure ofras-p21 as the basis for the modeling using a stepwise procedure in which identical and homologous amino acid residues in rap-1A are assumed to adopt the same conformation as the corresponding residues in p21. Side-chain conformations for homologous and nonhomologous residues are generated in conformations that are as close as possible to those of the corresponding side chains in p21. The entire structure has been subjected to a nested series of energy minimizations. The final predicted structure has an overall backbone deviation of 0.7 å from that ofras-p21. The effector binding domains from residues 32–47 are identical in both proteins (except for different side chains of different residues at position 45). A major difference occurs in the insertion region at residue 120. This region is in the middle of another effector loop of the p21 protein involving residues 115–126. Differences in sequence and structure in this region may contribute to the differences in cellular functions of these two proteins. 相似文献
106.
107.
Summary Microorganisms were able to remove hydrocarbons (pentane and isobutane) from air by biological action in a columnar bioreactor with ceramic packing. The reactor was operated in a liquid continuous mode with gas recirculation and a slow addition of the organic-containing air. After a period of acclimation, the reactor has operated for 12 months with only pentane and isobutane as carbon sources. The gaseous hydrocarbons have been degraded throughout this period. The hydrocarbon removal rates measured between 1 and 2 g h–1 m–3. The microbes were shown to be able to degrade these gaseous hydrocarbons completely in a closed bioreactor without any additional nutrients.Research supported by the Advanced Industrial Concepts Division-Biological and Chemical Technologies Research. U.S. Department of Energy, under contract DE-AC05-84OR21400 with Martin Marietta Energy Systems. Inc. 相似文献
108.
109.
Cholera toxin (CT) stimulated phospholipase activity and caused [3H]arachidonic acid (3H-AA) release in a murine macrophage/monocyte cell line. Pretreatment of cells with dexamethasone, a phospholipase A2 (PLA2) inhibitor, did not affect CT-induced 3H-AA release. In contrast, aspirin, which is an inhibitor of phospholipase C (PLC), blocked CT-induced 3H-AA release and subsequent prostaglandin (PC) synthesis. The inhibitory effect of aspirin was dose dependent, with 4 mM reducing the CT response by approximately 50%. Similarly, inhibition was time dependent, occurring when the drug was added to the culture medium as late as 30 min after CT. Brief exposure (30 min) of the cells to aspirin did not alter their subsequent response to CT, but 3H-AA release from cells exposed to aspirin for 2.5 h was irreversibly inhibited. The data suggested that CT stimulation of AA metabolism may involve increased PLC activity. 相似文献
110.
Corinna Richter Ron L. Dy Rebecca E. McKenzie Bridget N.J. Watson Corinda Taylor James T. Chang Matthew B. McNeil Raymond H.J. Staals Peter C. Fineran 《Nucleic acids research》2014,42(13):8516-8526
Clustered regularly interspaced short palindromic repeats (CRISPR), in combination with CRISPR associated (cas) genes, constitute CRISPR-Cas bacterial adaptive immune systems. To generate immunity, these systems acquire short sequences of nucleic acids from foreign invaders and incorporate these into their CRISPR arrays as spacers. This adaptation process is the least characterized step in CRISPR-Cas immunity. Here, we used Pectobacterium atrosepticum to investigate adaptation in Type I-F CRISPR-Cas systems. Pre-existing spacers that matched plasmids stimulated hyperactive primed acquisition and resulted in the incorporation of up to nine new spacers across all three native CRISPR arrays. Endogenous expression of the cas genes was sufficient, yet required, for priming. The new spacers inhibited conjugation and transformation, and interference was enhanced with increasing numbers of new spacers. We analyzed ∼350 new spacers acquired in priming events and identified a 5′-protospacer-GG-3′ protospacer adjacent motif. In contrast to priming in Type I-E systems, new spacers matched either plasmid strand and a biased distribution, including clustering near the primed protospacer, suggested a bi-directional translocation model for the Cas1:Cas2–3 adaptation machinery. Taken together these results indicate priming adaptation occurs in different CRISPR-Cas systems, that it can be highly active in wild-type strains and that the underlying mechanisms vary. 相似文献