全文获取类型
收费全文 | 47174篇 |
免费 | 4853篇 |
国内免费 | 1769篇 |
出版年
2024年 | 42篇 |
2023年 | 344篇 |
2022年 | 651篇 |
2021年 | 1579篇 |
2020年 | 1123篇 |
2019年 | 1387篇 |
2018年 | 1463篇 |
2017年 | 1097篇 |
2016年 | 1634篇 |
2015年 | 2382篇 |
2014年 | 2701篇 |
2013年 | 2951篇 |
2012年 | 3351篇 |
2011年 | 3156篇 |
2010年 | 1946篇 |
2009年 | 1739篇 |
2008年 | 2136篇 |
2007年 | 1950篇 |
2006年 | 1762篇 |
2005年 | 1504篇 |
2004年 | 1277篇 |
2003年 | 1179篇 |
2002年 | 991篇 |
2001年 | 2675篇 |
2000年 | 2416篇 |
1999年 | 1854篇 |
1998年 | 655篇 |
1997年 | 705篇 |
1996年 | 625篇 |
1995年 | 553篇 |
1994年 | 473篇 |
1993年 | 369篇 |
1992年 | 910篇 |
1991年 | 756篇 |
1990年 | 614篇 |
1989年 | 488篇 |
1988年 | 378篇 |
1987年 | 340篇 |
1986年 | 254篇 |
1985年 | 202篇 |
1984年 | 135篇 |
1983年 | 101篇 |
1982年 | 80篇 |
1981年 | 67篇 |
1980年 | 48篇 |
1979年 | 55篇 |
1978年 | 44篇 |
1976年 | 41篇 |
1974年 | 42篇 |
1972年 | 40篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
51.
An insect larval toxin designated CryII is produced by several subspecies of Bacillus thuringiensis and differs from the other major delta-endotoxins in these bacteria in its size, toxicity profile and presence as part of an operon with three open reading frames (ORF). Such an operon from a novel B. thuringiensis isolate has been cloned and differs from one previously characterized in the following ways: (a) the size and number of amino acid repeats in one of the ORFs; (b) the smaller size of the CryII protoxin and the presence of a unique 110-kDa CryII-related antigen; and (c) high larvicidal activity for a particular Lepidopteran but low activity for a Dipteran. Various subclones of this operon were introduced into a plasmid-free B. thuringiensis strain and only the cryII gene was found to be necessary for protoxin accumulation. 相似文献
52.
Wei Liu Yaoting Sun Weigang Ge Fangfei Zhang Lin Gan Yi Zhu Tiannan Guo Kexin Liu 《Molecular & cellular proteomics : MCP》2022,21(2):100187
Drug resistance is a critical obstacle to effective treatment in patients with chronic myeloid leukemia. To understand the underlying resistance mechanisms in response to imatinib mesylate (IMA) and adriamycin (ADR), the parental K562 cells were treated with low doses of IMA or ADR for 2 months to generate derivative cells with mild, intermediate, and severe resistance to the drugs as defined by their increasing resistance index. PulseDIA-based (DIA [data-independent acquisition]) quantitative proteomics was then employed to reveal the proteome changes in these resistant cells. In total, 7082 proteins from 98,232 peptides were identified and quantified from the dataset using four DIA software tools including OpenSWATH, Spectronaut, DIA-NN, and EncyclopeDIA. Sirtuin signaling pathway was found to be significantly enriched in both ADR-resistant and IMA-resistant K562 cells. In particular, isocitrate dehydrogenase (NADP(+)) 2 was identified as a potential drug target correlated with the drug resistance phenotype, and its inhibition by the antagonist AGI-6780 reversed the acquired resistance in K562 cells to either ADR or IMA. Together, our study has implicated isocitrate dehydrogenase (NADP(+)) 2 as a potential target that can be therapeutically leveraged to alleviate the drug resistance in K562 cells when treated with IMA and ADR. 相似文献
53.
54.
A frameshift mutation (2869insG) in the second transmembrane domain of the CFTR gene: identification, regional distribution, and clinical presentation.
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
55.
A. Doisy S. Paillasson P. Tracqui F. Germain F. Leitner M. Robert-Nicoud X. Ronot 《Cell biology and toxicology》1996,12(4-6):363-366
The organization of eukaryotic chromatin is not static but changes as a function of cell status during processes such as proliferation, differentiation, and migration. DNA quantification has not been used extensively to investigate chromatin dynamics in combination with cellular migration. In this context, an optimized DNA-specific, nonperturbant method has been developed for studying chromatin organization, using the fluorescent vital bisbenzimidazole probe Hoechst 33342: this property has been described by Hamori et al. (1980). Computer-assisted image analysis was used to follow migratory activity and chromatin organization of L929 fibroblasts during in vitro wound healing. Cell movements were analyzed using an optical flow technique, which consists in the calculation of the velocity field of cells and nuclear movements in the frame. This system allows the correlation of cell migration and position in the cell cycle. It makes it possible to study chromatin dynamics using a quantitative analysis of nuclear differentiation reorganization (nuclear texture) and to correlate this with migration characteristics. The present system would be of interest for studying cell-extracellular matrix interactions using differing substrates, and also the migratory response to chemotactic factors. Such a model is a prerequisite for gaining better understanding of drug action. 相似文献
56.
57.
58.
W. D. Roof H. Q. Fang K. D. Young Jianling Sun & Ry Young 《Molecular microbiology》1997,25(6):1031-1046
slyD encodes a 196 amino acid polypeptide that is a member of the FKBP family of cis–trans peptidyl–prolyl isomerases (PPIases). slyD mutations affect plaque formation by the phage φX174 by blocking the action of the phage lysis protein E. Here we describe the selection of a set of spontaneous slyD mutations conferring resistance to the expression of gene E from a plasmid. These mutations occur disproportionately in residues of SlyD that, based on the structure of the prototype mammalian FKBP12, make ligand contacts with immunosuppressing drug molecules or are conserved in other FKBP proteins. A wide variation in the plating efficiency of φX174 on these E R strains is observed, relative to the parental, indicating that these alleles differ widely in residual SlyD activity. Moreover, it is found that slyD mutations cause significant growth rate defects in Escherichia coli B and C backgrounds. Finally, overexpression of slyD causes filamentation of the host. Thus, among the FKBP genes found in organisms across the evolutionary spectrum, slyD is unique in having three distinct drug-independent phenotypes. 相似文献
59.
A. Benito E. Viaplana J.L. Corchero X. Carbonell A. Villaverde 《FEMS microbiology letters》1995,129(2-3):157-162
Abstract The 3D gene of foot-and-mouth disease virus encodes the viral RNA dependent RNA polymerase, also called virus infection associated (VIA) antigen, which is the most important serological marker of virus infection. This 3D gene from a serotype Cl virus has been cloned and overexpressed in Escherichia coli under the control of the strong lambda lytic promoters. The resulting 51 kDa recombinant protein has been shown to be immunoreactive with sera from infected animals. After induction of gene expression, an immediate and dramatic arrest of cell DNA synthesis occurs, similar to that produced by genotoxic doses of the drug mitomycin C. This effect does not occur during the production of either a truncated VIA antigen or other related and non-related viral proteins. The inhibition of DNA replication results in a subsequent induction of the host SOS DNA-repair response and in an increase of the mutation frequency in the surviving cells. 相似文献
60.