全文获取类型
收费全文 | 2824篇 |
免费 | 160篇 |
国内免费 | 1篇 |
出版年
2023年 | 21篇 |
2022年 | 19篇 |
2021年 | 79篇 |
2020年 | 45篇 |
2019年 | 70篇 |
2018年 | 99篇 |
2017年 | 83篇 |
2016年 | 115篇 |
2015年 | 175篇 |
2014年 | 156篇 |
2013年 | 214篇 |
2012年 | 234篇 |
2011年 | 225篇 |
2010年 | 145篇 |
2009年 | 144篇 |
2008年 | 184篇 |
2007年 | 158篇 |
2006年 | 141篇 |
2005年 | 139篇 |
2004年 | 121篇 |
2003年 | 96篇 |
2002年 | 85篇 |
2001年 | 34篇 |
2000年 | 21篇 |
1999年 | 34篇 |
1998年 | 21篇 |
1997年 | 13篇 |
1996年 | 12篇 |
1995年 | 9篇 |
1994年 | 11篇 |
1993年 | 5篇 |
1992年 | 9篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 6篇 |
1988年 | 6篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1984年 | 7篇 |
1983年 | 5篇 |
1982年 | 6篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1976年 | 3篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1970年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有2985条查询结果,搜索用时 171 毫秒
1.
Michael H Woo John R Vance Ana R Otero Marcos Christian Bailly Mary-Ann Bjornsti 《The Journal of biological chemistry》2002,277(6):3813-3822
DNA topoisomerase I (Top1p) catalyzes topological changes in DNA and is the cellular target of the antitumor agent camptothecin (CPT). Non-CPT drugs that target Top1p, such as indolocarbazoles, are under clinical development. However, whether the cytotoxicity of indolocarbazoles derives from Top1p poisoning remains unclear. To further investigate indolocarbazole mechanism, rebeccamycin R-3 activity was examined in vitro and in yeast. Using a series of Top1p mutants, where substitution of residues around the active site tyrosine has well-defined effects on enzyme catalysis, we show that catalytically active, CPT-resistant enzymes remain sensitive to R-3. This indolocarbazole did not inhibit yeast Top1p activity, yet was effective in stabilizing Top1p-DNA complexes. Similar results were obtained with human Top1p, when Ser or His were substituted for Asn-722. The mutations altered enzyme function and sensitivity to CPT, yet R-3 poisoning of Top1p was unaffected. Moreover, top1delta, rad52delta yeast cells expressing human Top1p, but not catalytically inactive Top1Y723Fp, were sensitive to R-3. These data support hTop1p as the cellular target of R-3 and indicate that distinct drug-enzyme interactions at the active site are required for efficient poisoning by R-3 or CPT. Furthermore, resistance to one poison may potentiate cell sensitivity to structurally distinct compounds that also target Top1p. 相似文献
2.
3.
4.
The present study was carried out to evaluate the suitability of the unstable white-zeste system in Drosophila melanogaster by testing 4 organophosphorus insecticides for potential genotoxic activity: dimethoate, fenitrothion, malathion, and methyl parathion. In view of the high sensitivity to insecticides of the unstable zeste strain used in this assay and the negative results obtained in this work, the white-zeste system does not appear to be sufficiently accurate for the evaluation of the mutagenic potential of specifically toxic chemicals, like insecticides. 相似文献
5.
To extend the data on the mutagenic effects of intercalating agents in Drosophila melanogaster, chloroquine and quinacrine were tested for the induction of genetic damage in D. melanogaster males. Sex-linked recessive lethals and sex-chromosome loss induction were studied following treatment of adult males using a feeding technique. Our results show that both intercalating compounds increase significantly the frequency of sex-linked recessive lethals, but are unable to induce sex-chromosome loss in male germ cells under the conditions of testing. 相似文献
6.
The monoamine transporter of the chromaffin granule membranes can be specifically labeled by the photoaffinity reagent 7-azido-8-[125I]iodoketanserin. The characteristics of the labeled protein have been investigated. Two-dimensional gel electrophoresis of the labeled membranes indicated a MW of about 70,000 and an isoelectric point ranging from 3.8 to 4.6. No clear protein spot was associated with the radioactive material, which migrated between glycoproteins GPII and GPIV. The diffuse aspect of the radioactive material indicated a heterogeneity, which was not modified after a second electrophoresis. This heterogeneity was, at least partially, due to glycosylation of the transporter; neuraminidase treatment increased the protein pI up to 6.3, whereas digestion with N-glycopeptidase markedly decreased the apparent MW, from 70,000 to 50,000. SDS-polyacrylamide gel electrophoresis showed that, at low acrylamide concentrations, the labeled material migrated more rapidly than predicted from the mobility of the markers of molecular weight, a behavior which indicated a marked hydrophobicity of the transporter. The labeled protein was purified to homogeneity by a combination of chromatography on DEAE-cellulose at pH 4.5, on immobilized wheat germ agglutinin, and on hydroxylapatite in the presence of SDS. During this purification, the specific radioactivity was increased by a factor of 300-500, with a yield of 10-20%. 相似文献
7.
Molecular control mechanisms of lysine and threonine biosynthesis in amino acid-producing corynebacteria: Redirecting carbon flow 总被引:3,自引:0,他引:3
Abstract Threonine and lysine are two of the economically most important essential amino acids. They are produced industrially by species of the genera Corynebacterium and Brevibacterium . The branched biosynthetic pathway of these amino acids in corynebacteria is unusual in gene organization and in the control of key enzymatic steps with respect to other microorganisms. This article reviews the molecular control mechanisms of the biosynthetic pathways leading to threonine and lysine in corynebacteria, and their implications in the production of these amino acids. Carbon flux can be redirected at branch points by gene disruption of the competing pathways for lysine or threonine. Removal of bottlenecks has been achieved by amplification of genes which encode feedback resistant aspartokinase and homoserine dehydrogenase (obtained by in vitro directed mutagenesis). 相似文献
8.
Graciela C. Theiler Yanina C. Marcos Edgardo Kolkowski Nancy Lindel Mónica Capucchio Paula Barrionuevo Francisco R. Carnese M. Leonardo Satz 《Immunogenetics》1996,43(6):398-399
The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession number U17107. The nameB*3509 was officially assigned by the WHO Nomenclature Committee in December 1994 相似文献
9.
P. Marcos R. Coveas J.A. Narvez G. Tramu J.A. Aguirre S. Gonzlez-Barn 《Peptides》1993,14(6):1263-1269
This paper examines the distribution of fibers and cell bodies containing alpha-neo-endorphin in the cat brain stem by using an indirect immunoperoxidase technique. A high or moderate density of immunoreactive cell bodies was found in the superior central nucleus, nucleus incertus, dorsal tegmental nucleus, nucleus of the trapezoid body, and in the laminar spinal trigeminal nucleus, whereas a low density of such perikarya was observed in the inferior colliculus, nucleus praepositus hypoglossi, dorsal nucleus of the raphe, nucleus of the brachium of the inferior colliculus, and in the nucleus of the solitary tract. The highest density of immunoreactive fibers was found in the substantia nigra, dorsal motor nucleus of the vagus, nucleus coeruleus, lateral tegmental field, marginal nucleus of the brachium conjunctivum, and in the inferior and medial vestibular nuclei. These results indicate that alpha-neo-endorphin is widely distributed in the cat brain stem and suggest that the peptide could play an important role in several physiological functions, e.g., those involved in respiratory, cardiovascular, auditory, and motor mechanisms. 相似文献
10.
Martina Ferraguti Sergio Magallanes Jéssica Jiménez-Peñuela Josué Martínez-de la Puente Luz Garcia-Longoria Jordi Figuerola Jaime Muriel Tamer Albayrak Staffan Bensch Camille Bonneaud Rohan H. Clarke Gábor Á. Czirják Dimitar Dimitrov Kathya Espinoza John G. Ewen Farah Ishtiaq Wendy Flores-Saavedra László Zsolt Garamszegi Olof Hellgren Dita Horakova Kathryn P. Huyvaert Henrik Jensen Asta Križanauskienė Marcos R. Lima Charlene Lujan-Vega Eyðfinn Magnussen Lynn B. Martin Kevin D. Matson Anders Pape Møller Pavel Munclinger Vaidas Palinauskas Péter L. Pap Javier Pérez-Tris Swen C. Renner Robert Ricklefs Sergio Scebba Ravinder N. M. Sehgal Manuel Soler Eszter Szöllősi Gediminas Valkiūnas Helena Westerdahl Pavel Zehtindjiev Alfonso Marzal 《Global Ecology and Biogeography》2023,32(5):809-823