全文获取类型
收费全文 | 39178篇 |
免费 | 3689篇 |
国内免费 | 29篇 |
专业分类
42896篇 |
出版年
2024年 | 39篇 |
2023年 | 213篇 |
2022年 | 479篇 |
2021年 | 1071篇 |
2020年 | 546篇 |
2019年 | 746篇 |
2018年 | 846篇 |
2017年 | 751篇 |
2016年 | 1268篇 |
2015年 | 2137篇 |
2014年 | 2296篇 |
2013年 | 2536篇 |
2012年 | 3432篇 |
2011年 | 3399篇 |
2010年 | 2157篇 |
2009年 | 1815篇 |
2008年 | 2572篇 |
2007年 | 2541篇 |
2006年 | 2265篇 |
2005年 | 2150篇 |
2004年 | 2049篇 |
2003年 | 1784篇 |
2002年 | 1657篇 |
2001年 | 298篇 |
2000年 | 175篇 |
1999年 | 310篇 |
1998年 | 368篇 |
1997年 | 232篇 |
1996年 | 205篇 |
1995年 | 178篇 |
1994年 | 159篇 |
1993年 | 160篇 |
1992年 | 128篇 |
1991年 | 119篇 |
1990年 | 106篇 |
1989年 | 98篇 |
1988年 | 71篇 |
1987年 | 79篇 |
1986年 | 61篇 |
1985年 | 89篇 |
1984年 | 88篇 |
1983年 | 97篇 |
1982年 | 101篇 |
1981年 | 93篇 |
1980年 | 94篇 |
1979年 | 50篇 |
1978年 | 81篇 |
1977年 | 56篇 |
1976年 | 50篇 |
1975年 | 42篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
1.
2.
A putative GDP–GTP exchange factor is required for development of the excretory cell in Caenorhabditis elegans 下载免费PDF全文
Norio Suzuki Matthew Buechner Kiyoji Nishiwaki David H. Hall Hiroyuki Nakanishi Yoshimi Takai Naoki Hisamoto Kunihiro Matsumoto 《EMBO reports》2001,2(6):530-535
The Caenorhabditis elegans excretory cell extends tubular processes, called canals, along the basolateral surface of the epidermis. Mutations in the exc-5 gene cause tubulocystic defects in this canal. Ultrastructural analysis suggests that exc-5 is required for the proper placement of cytoskeletal elements at the apical epithelial surface. exc-5 encodes a protein homologous to guanine nucleotide exchange factors and contains motif architecture similar to that of FGD1, which is responsible for faciogenital dysplasia. exc-5 interacts genetically with mig-2, which encodes Rho GTPase. These results suggest that EXC-5 controls the structural organization of the excretory canal by regulating Rho family GTPase activities. 相似文献
3.
4.
5.
David M. Anderson Richard H. Scheller James W. Posakony Linda B. McAllister Steven G. Trabert Clifford Beall Roy J. Britten Eric H. Davidson 《Journal of molecular biology》1981,145(1):5-28
Three repetitive sequence families from the sea urchin genome were studied, each defined by homology with a specific cloned probe one to a few hundred nucleotides long. Recombinant λ-sea urchin DNA libraries were screened with these probes, and individual recombinants were selected that include genomic members of these families. Restriction mapping, gel blot, and kinetic analyses were carried out to determine the organization of each repeat family. Sequence elements belonging to the first of the three repeat families were found to be embedded in longer repeat sequences. These repeat sequences frequently occur in small clusters. Members of the second repeat family are also found in a long repetitive sequence environment, but these repeats usually occur singly in any given region of the DNA. The sequences of the third repeat are only 200 to 300 nucleotides long, and are generally terminated by single copy DNA, though a few examples were found associated with other repeats. These three repeat sequence families constitute sets of homologous sequence elements that relate distant regions of the DNA. 相似文献
6.
Tanner Miest Dyana Saenz Anne Meehan Manuel Llano Eric M. Poeschla 《Methods (San Diego, Calif.)》2009,47(4):298-303
RNAi is a powerful technology for analyzing gene function in human cells. However, its utility can be compromised by inadequate knockdown of the target mRNA or by interpretation of effects without rigorous controls. We review lentiviral vector-based methods that enable transient or stable knockdowns to trace mRNA levels in human CD4+ T cell lines and other targets. Critical controls are reviewed, including rescue of the pre-knockdown phenotype by re-expression of the targeted gene. The time from thinking about a potential knockdown target to analysis of phenotypes can be as short as a few weeks. 相似文献
7.
8.
Siew Choo Lim Matthew W. Bowler Ting Feng Lai Haiwei Song 《Nucleic acids research》2012,40(21):11009-11022
Mutations in immunoglobulin µ-binding protein 2 (Ighmbp2) cause distal spinal muscular atrophy type 1 (DSMA1), an autosomal recessive disease that is clinically characterized by distal limb weakness and respiratory distress. However, despite extensive studies, the mechanism of disease-causing mutations remains elusive. Here we report the crystal structures of the Ighmbp2 helicase core with and without bound RNA. The structures show that the overall fold of Ighmbp2 is very similar to that of Upf1, a key helicase involved in nonsense-mediated mRNA decay. Similar to Upf1, domains 1B and 1C of Ighmbp2 undergo large conformational changes in response to RNA binding, rotating 30° and 10°, respectively. The RNA binding and ATPase activities of Ighmbp2 are further enhanced by the R3H domain, located just downstream of the helicase core. Mapping of the pathogenic mutations of DSMA1 onto the helicase core structure provides a molecular basis for understanding the disease-causing consequences of Ighmbp2 mutations. 相似文献
9.
10.
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