全文获取类型
收费全文 | 17191篇 |
免费 | 1168篇 |
国内免费 | 2114篇 |
出版年
2024年 | 82篇 |
2023年 | 427篇 |
2022年 | 542篇 |
2021年 | 779篇 |
2020年 | 786篇 |
2019年 | 870篇 |
2018年 | 774篇 |
2017年 | 655篇 |
2016年 | 723篇 |
2015年 | 923篇 |
2014年 | 999篇 |
2013年 | 1575篇 |
2012年 | 695篇 |
2011年 | 700篇 |
2010年 | 594篇 |
2009年 | 677篇 |
2008年 | 679篇 |
2007年 | 642篇 |
2006年 | 679篇 |
2005年 | 687篇 |
2004年 | 574篇 |
2003年 | 509篇 |
2002年 | 548篇 |
2001年 | 357篇 |
2000年 | 318篇 |
1999年 | 312篇 |
1998年 | 309篇 |
1997年 | 278篇 |
1996年 | 268篇 |
1995年 | 256篇 |
1994年 | 263篇 |
1993年 | 236篇 |
1992年 | 213篇 |
1991年 | 171篇 |
1990年 | 156篇 |
1989年 | 136篇 |
1988年 | 143篇 |
1987年 | 103篇 |
1986年 | 111篇 |
1985年 | 101篇 |
1984年 | 136篇 |
1983年 | 79篇 |
1982年 | 93篇 |
1981年 | 68篇 |
1980年 | 66篇 |
1979年 | 60篇 |
1978年 | 29篇 |
1977年 | 27篇 |
1976年 | 25篇 |
1973年 | 11篇 |
排序方式: 共有10000条查询结果,搜索用时 359 毫秒
1.
Bugreev D. V. Sinitsyna O. I. Buneva V. N. Nevinsky G. A. 《Russian Journal of Bioorganic Chemistry》2003,29(3):249-261
Data on the interaction of DNA type I topoisomerases from the murine and human placenta cells with specific and nonspecific oligonucleotides of various structures and lengths are summarized. The relative contributions of various contacts between the enzymes and DNA that have previously been detected by X-ray analysis to the total affinity of the topoisomerases for DNA substrates are estimated. Factors that determine the differences in the enzyme interactions with specific and nonspecific single- and double-stranded DNAs are revealed. The results of the X-ray analysis of human DNA topoisomerase I are interpreted taking into account data on the comprehensive thermodynamic and kinetic analysis of the enzyme interaction with the specific and nonspecific DNAs. 相似文献
2.
3.
《Journal of molecular biology》2021,433(4):166764
Apical sodium-dependent bile acid transporter (ASBT) catalyses uphill transport of bile acids using the electrochemical gradient of Na+ as the driving force. The crystal structures of two bacterial homologues ASBTNM and ASBTYf have previously been determined, with the former showing an inward-facing conformation, and the latter adopting an outward-facing conformation accomplished by the substitution of the critical Na+-binding residue glutamate-254 with an alanine residue. While the two crystal structures suggested an elevator-like movement to afford alternating access to the substrate binding site, the mechanistic role of Na+ and substrate in the conformational isomerization remains unclear. In this study, we utilized site-directed alkylation monitored by in-gel fluorescence (SDAF) to probe the solvent accessibility of the residues lining the substrate permeation pathway of ASBTNM under different Na+ and substrate conditions, and interpreted the conformational states inferred from the crystal structures. Unexpectedly, the crosslinking experiments demonstrated that ASBTNM is a monomer protein, unlike the other elevator-type transporters, usually forming a homodimer or a homotrimer. The conformational dynamics observed by the biochemical experiments were further validated using DEER measuring the distance between the spin-labelled pairs. Our results revealed that Na+ ions shift the conformational equilibrium of ASBTNM toward the inward-facing state thereby facilitating cytoplasmic uptake of substrate. The current findings provide a novel perspective on the conformational equilibrium of secondary active transporters. 相似文献
4.
Joseph V. Rodricks 《人类与生态风险评估》2014,20(1):3-28
The publication in 1962 of Rachel Carson's Silent Spring marks the mid-point in a century that saw, in its first half, the emergence of public health concerns related to human exposures to chemicals, and, in its second half, the emergence of public policies to deal with those concerns. Those policies made it imperative that the scientific community come to grips with the problem of identifying exposure levels not likely to cause harm. This problem was not significantly discussed within the scientific community until the 1950s, and well-described methods for practical solutions to it did not appear until the 1970s. An important report from the National Academy of Sciences, published in 1983 (Risk Assessment in the Federal Government), provided an analysis of these emerging methods, and recommended a useful framework for the assessment and management of risk. This framework remains central to public health and regulatory decision-making. A high-level perspective is offered on events leading to and following the 1983 report. The article describes early thinking about chemical toxicity and the scientific path that thinking followed through the 20th century, and to the present. 相似文献
5.
6.
7.
Larvae and nymphs of the tick Ixodes ricinus L. display similar reactions to analogs of the insect juvenile hormones (methoprene and pyriproxyfen), which induce at both stages juvenalization of the Haller's sense organ regenerates. Similar effects were also described for retinoic acid. Unlike juvenoids, retinoic acid can affect not only regeneration, but also normal development of the Haller's organ and cause changes corresponding to so-called regenerative induction. Amputation of the leg and treatment with retinoic acid do not affect the duration of larval or nymphal development, while juvenoids somewhat accelerate their development. 相似文献
8.
Eric M. Koehn 《Archives of biochemistry and biophysics》2010,493(1):96-10494
For several decades only one chemical pathway was known for the de novo biosynthesis of the essential DNA nucleotide, thymidylate. This reaction catalyzed by thyA or TYMS encoded thymidylate synthases is the last committed step in the biosynthesis of thymidylate and proceeds via the reductive methylation of uridylate. However, many microorganisms have recently been shown to produce a novel, flavin-dependent thymidylate synthase encoded by the thyX gene. Preliminary structural and mechanistic studies have shown substantial differences between these deoxyuridylate-methylating enzymes. Recently, both the chemical and kinetic mechanisms of FDTS have provided further insight into the distinctions between thyA and thyX encoded thymidylate synthases. Since FDTSs are found in several severe human pathogens their unusual mechanism offers a promising future for the development of antibiotic and antiviral drugs with little effect on human thymidylate biosynthesis. 相似文献
9.
10.
Splenic gene expression profiling in White Leghorn layer inoculated with the Salmonella enterica serovar Enteritidis 下载免费PDF全文
Salmonella enterica serovar Enteritidis (SE) is a foodborne pathogen that can threaten human health through contaminated poultry products. Live poultry, chicken eggs and meat are primary sources of human salmonellosis. To understand the genetic resistance of egg‐type chickens in response to SE inoculation, global gene expression in the spleen of 20‐week‐old White Leghorn was measured using the Agilent 4 × 44 K chicken microarray at 7 and 14 days following SE inoculation (dpi). Results showed that there were 1363 genes significantly differentially expressed between inoculated and non‐inoculated groups at 7 dpi (I7/N7), of which 682 were up‐regulated and 681 were down‐regulated genes. By contrast, 688 differentially expressed genes were observed at 14 dpi (I14/N14), of which 371 were up‐regulated genes and 317 were down‐regulated genes. There were 33 and 28 immune‐related genes significantly differentially expressed in the comparisons of I7/N7 and I14/N14 respectively. Functional annotation revealed that several Gene Ontology (GO) terms related to immunity were significantly enriched between the inoculated and non‐inoculated groups at 14 dpi but not at 7 dpi, despite a similar number of immune‐related genes identified between I7/N7 and I14/N14. The immune response to SE inoculation changes with different time points following SE inoculation. The complicated interaction between the immune system and metabolism contributes to the immune responses to SE inoculation of egg‐type chickens at 14 dpi at the onset of lay. GC, TNFSF8, CD86, CD274, BLB1 and BLB2 play important roles in response to SE inoculation. The results from this study will deepen the current understanding of the genetic response of the egg‐type chicken to SE inoculation at the onset of egg laying. 相似文献