全文获取类型
收费全文 | 5551篇 |
免费 | 148篇 |
国内免费 | 184篇 |
专业分类
5883篇 |
出版年
2024年 | 3篇 |
2023年 | 50篇 |
2022年 | 88篇 |
2021年 | 124篇 |
2020年 | 69篇 |
2019年 | 94篇 |
2018年 | 128篇 |
2017年 | 89篇 |
2016年 | 75篇 |
2015年 | 95篇 |
2014年 | 490篇 |
2013年 | 646篇 |
2012年 | 413篇 |
2011年 | 309篇 |
2010年 | 209篇 |
2009年 | 276篇 |
2008年 | 282篇 |
2007年 | 301篇 |
2006年 | 239篇 |
2005年 | 257篇 |
2004年 | 205篇 |
2003年 | 168篇 |
2002年 | 154篇 |
2001年 | 101篇 |
2000年 | 91篇 |
1999年 | 96篇 |
1998年 | 103篇 |
1997年 | 62篇 |
1996年 | 61篇 |
1995年 | 76篇 |
1994年 | 101篇 |
1993年 | 64篇 |
1992年 | 55篇 |
1991年 | 35篇 |
1990年 | 37篇 |
1989年 | 21篇 |
1988年 | 30篇 |
1987年 | 16篇 |
1986年 | 22篇 |
1985年 | 25篇 |
1984年 | 22篇 |
1983年 | 26篇 |
1982年 | 23篇 |
1981年 | 10篇 |
1980年 | 4篇 |
1979年 | 14篇 |
1978年 | 13篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1973年 | 3篇 |
排序方式: 共有5883条查询结果,搜索用时 15 毫秒
61.
Xia S Wang M Lee HR Sinha A Blaha G Christian T Wang J Konigsberg W 《Journal of molecular biology》2011,406(4):558-10149
We have previously observed that stepwise replacement of amino acid residues in the nascent base-pair binding pocket of RB69 DNA polymerase (RB69pol) with Ala or Gly expanded the space in this pocket, resulting in a progressive increase in misincorporation. However, in vivo results with similar RB69pol nascent base-pair binding pocket mutants showed that mutation rates, as determined by the T4 phage rI forward assay and rII reversion assay, were significantly lower for the RB69pol S565G/Y567A double mutant than for the Y567A single mutant, the opposite of what we would have predicted. To investigate the reasons for this unexpected result, we have determined the pre-steady-state kinetic parameters and crystal structures of relevant ternary complexes. We found that the S565G/Y567A mutant generally had greater base selectivity than the Y567A mutant and that the kinetic parameters for dNMP insertion, excision of the 3′-terminal nucleotide residue, and primer extension beyond a mispair differed not only between these two mutants but also between the two highly mutable sequences in the T4 rI complementary strand. Comparison of the crystal structures of these two mutants with correct and incorrect incoming dNTPs provides insight into the unexpected increase in the fidelity of the S565G/Y567A double mutant. Taken together, the kinetic and structural results provide a basis for integrating and interpreting in vivo and in vitro observations. 相似文献
62.
Cortez MR Pinho AP Cuervo P Alfaro F Solano M Xavier SC D'Andrea PS Fernandes O Torrico F Noireau F Jansen AM 《Experimental parasitology》2006,114(4):305-313
An active Trypanosoma cruzi transmission cycle maintained by wild rodents in the Andean valleys of Cochabamba Bolivia is described. Wild and domestic Triatoma infestans with 60% infection with T. cruzi were found and was evidenced in 47.5% (rodents) and 26.7% (marsupial) by parasitological and/or serologycal methods. Phyllotis ocilae and the marsupial species Thylamys elegans, are the most important reservoirs followed by Bolomys lactens and Akodon boliviensis. In spite of both genotypes (TCI and TCII) being prevalent in Bolivia, in our study area only T. cruzi I is being transmitted. Our data suggest that wild T. infestans and wild small mammals play an important role in the maintenance of the transmission cycle of T. cruzi. Furthermore, the finding of high prevalence of T. cruzi infection in wild T. infestans point to the risk of the dispersion of Chagas' disease. 相似文献
63.
滚环DNA扩增的原理、应用和展望 总被引:2,自引:0,他引:2
滚环DNA扩增 (rollingcircleDNAamplification ,RCA)是一种等温信号扩增方法 ,其线性扩增倍数为 1 0 5,指数化扩增能力大于 109,产生的扩增产物连接在固相支持物 (如玻片、微孔板等 )表面的DNA引物或抗体上。RCA是一种适合在芯片上 (on chip)进行信号扩增的新技术 ,它既能提供研究分析的敏感性和特异性 ,又能保持立体分析的多元性。RCA亦是一种痕量的分子检测方法 ,可用于极其微量的生物大分子和生物标志的检测与研究 相似文献
64.
65.
66.
Hidetaka Suzuki Seiko YamadaYoshiharu Toyama Shigeki Takeda 《Biochimica et Biophysica Acta - Proteins and Proteomics》2010,1804(9):1738-1742
The Mu phage virion contains tail-spike proteins beneath the baseplate, which it uses to adsorb to the outer membrane of Escherichia coli during the infection process. The tail spikes are composed of gene product 45 (gp45), which contains 197 amino acid residues. In this study, we purified and characterized both the full-length and the C-terminal domains of recombinant gp45 to identify the functional and structural domains. Limited proteolysis resulted in a Ser64-Gln197 sequence, which was composed of a stable C-terminal domain. Analytical ultracentrifugation of the recombinant C-terminal domain (gp45-C) indicated that the molecular weight of gp45-C was about 58 kDa and formed a trimeric protomer in solution. Coprecipitation experiments and a quartz crystal microbalance (QCM) demonstrated that gp45-C irreversibly binds to the E. coli membrane. These results indicate that gp45 shows behaviors similar to tail-spike proteins of other phages; however, gp45 did not show significant sequence homology with the other phage tail-spike structures that have been identified. 相似文献
67.
DNA damage created by endogenous or exogenous genotoxic agents can exist in multiple forms, and if allowed to persist, can promote genome instability and directly lead to various human diseases, particularly cancer, neurological abnormalities, immunodeficiency and premature aging. To avoid such deleterious outcomes, cells have evolved an array of DNA repair pathways, which carry out what is typically a multiple-step process to resolve specific DNA lesions and maintain genome integrity. To fully appreciate the biological contributions of the different DNA repair systems, one must keep in mind the cellular context within which they operate. For example, the human body is composed of non-dividing and dividing cell types, including, in the brain, neurons and glial cells. We describe herein the molecular mechanisms of the different DNA repair pathways, and review their roles in non-dividing and dividing cells, with an eye toward how these pathways may regulate the development of neurological disease. 相似文献
68.
Alexander R. Ball Jr. Yen-Yun ChenKyoko Yokomori 《Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms》2014,1839(3):191-202
Cohesins are conserved and essential Structural Maintenance of Chromosomes (SMC) protein-containing complexes that physically interact with chromatin and modulate higher-order chromatin organization. Cohesins mediate sister chromatid cohesion and cellular long-distance chromatin interactions affecting genome maintenance and gene expression. Discoveries of mutations in cohesin's subunits and its regulator proteins in human developmental disorders, so-called “cohesinopathies,” reveal crucial roles for cohesins in development and cellular growth and differentiation. In this review, we discuss the latest findings concerning cohesin's functions in higher-order chromatin architecture organization and gene regulation and new insight gained from studies of cohesinopathies. This article is part of a Special Issue entitled: Chromatin and epigenetic regulation of animal development. 相似文献
69.
Haruna Sakurai Satoshi TakaiKasumi Kawamura Yuji OguraYasuhide Yoshioka Katsumi Kawasaki 《Biochemical and biophysical research communications》2014
RecQ5, a member of the conserved RecQ DNA helicase family, is required for the maintenance of genome stability. The human RECQL5 gene is expressed ubiquitously in almost all tissues, with strong expression in the testes (Shimamoto et al., 2000). However, it remains to be elucidated in which cells RecQ5 is expressed and how RecQ5 functions in the testes. In this present study we analyzed the expression of RecQ5 in Drosophila testes. The RecQ5 protein was specifically expressed in germline cells in larval, pupal, and adult testes. Drosophila RecQ5 was localized in nuclei of male germline stem cells, spermatogoniablasts, spermatogonia, and early spermatocytes. As growth of the early spermatocyte proceeded, the amount of RecQ5 increased in the nuclei. However, before maturation of the spermatocyte, the level of RecQ5 declined. Thus, RecQ5 expression was regulated. Furthermore, we compared recq5 mutant testes with the wild-type ones. The most conspicuous alterations were swelling of the apical region of and an increase in the number of spermatocytes in the recq5 testis, suggesting a relative accumulation of spermatocytes in the recq5 mutant testes. Therefore, Drosophila RecQ5 may contribute to the proper progression from germline stem cells to spermatocytes for maintenance of genome stability. 相似文献
70.