全文获取类型
收费全文 | 3063篇 |
免费 | 175篇 |
国内免费 | 1篇 |
专业分类
3239篇 |
出版年
2023年 | 30篇 |
2022年 | 45篇 |
2021年 | 93篇 |
2020年 | 62篇 |
2019年 | 80篇 |
2018年 | 113篇 |
2017年 | 99篇 |
2016年 | 126篇 |
2015年 | 202篇 |
2014年 | 183篇 |
2013年 | 236篇 |
2012年 | 256篇 |
2011年 | 243篇 |
2010年 | 159篇 |
2009年 | 156篇 |
2008年 | 185篇 |
2007年 | 162篇 |
2006年 | 143篇 |
2005年 | 144篇 |
2004年 | 125篇 |
2003年 | 107篇 |
2002年 | 88篇 |
2001年 | 31篇 |
2000年 | 19篇 |
1999年 | 29篇 |
1998年 | 18篇 |
1997年 | 11篇 |
1996年 | 10篇 |
1995年 | 7篇 |
1994年 | 8篇 |
1993年 | 4篇 |
1992年 | 6篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 6篇 |
1988年 | 5篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1985年 | 4篇 |
1984年 | 7篇 |
1983年 | 3篇 |
1982年 | 4篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有3239条查询结果,搜索用时 15 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.
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
3.
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
4.
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
5.
João Ricardo Sato Claudinei Eduardo Biazoli Ana Paula Arantes Bueno Arthur Caye Pedro Mario Pan Marcos Santoro Jessica Honorato-Mauer Giovanni Abrahão Salum Marcelo Queiroz Hoexter Rodrigo Affonseca Bressan Andrea Parolin Jackowski Euripedes Constantino Miguel Sintia Belangero Luis Augusto Rohde 《Genes, Brain & Behavior》2023,22(2):e12838
6.
Several important fitness components in herbaceous perennial plants are commonly related to plant size: flowering probability, reproductive allocation and fecundity. However, evidence for such size-dependence of fitness components is mostly anecdotal and unconnected to other life history traits. Here we report size-dependence for flowering probability and reproductive allocation in 11 populations of Pinguicula vulgaris and relate it to environmental factors. Flowering probability was size-dependent in all populations of P. vulgaris , and indicated the existence of a threshold size for reproduction. Populations at low altitudes and in wet soils showed a significantly higher threshold size for reproduction. Reproductive mass was also size-dependent in all populations. We found considerable between-population differences in the slope and the intercept of the regression between plant size and reproductive mass. This variation was weakly related to the environmental factors measured. In general, relationships between different size-dependent fitness components were low. Instead of showing a covariation of traits, in line with interpretations in terms of life history "tactics", P. vulgaris seemed to independently vary each size-dependent fitness component in each locality. In particular, no significant relationship was found between threshold size for reproduction and the slope of size-dependent reproductive allocation, as predicted by previous authors. Neither we found a significant influence of somatic cost of reproduction on size-dependent fitness components. 相似文献
7.
Prof. Dr. Wolf-Christian Dullo Dr. Marcos Gektidis Prof. Dr. Stjepko Golubic Dr. Georg A. Heiss Dipl. Biol. Heike Kampmann Dr. William Kiene Dipl. Ökol. Dieter K. Kroll Dipl. Biol. Martin L. Kuhrau Dr. Gudrun Radtke Dr. John G. Reijmer Dr. Götz B. Reinicke Prof. Dr. Dietrich Schlichter Prof. Dr. Helmut Schuhmacher Klaus Vogel 《Facies》1995,32(1):145-188
8.
Castellani John W.; Maresh Carl M.; Armstrong Lawrence E.; Kenefick Robert W.; Riebe Deborah; Echegaray Marcos; Casa Douglas; Castracane V. Daniel 《Journal of applied physiology》1997,82(3):799-806
Castellani, John W., Carl M. Maresh, Lawrence E. Armstrong,Robert W. Kenefick, Deborah Riebe, Marcos Echegaray, Douglas Casa, andV. Daniel Castracane. Intravenous vs. oral rehydration: effects onsubsequent exercise-heat stress. J. Appl.Physiol. 82(3): 799-806, 1997.This studycompared the influence of intravenous vs. oral rehydration afterexercise-induced dehydration during a subsequent 90-min exercisebout. It was hypothesized that cardiovascular, thermoregulatory, and hormonal variables would be the same between intravenous and oral rehydration because of similar restoration ofplasma volume (PV) and osmolality (Osmo). Eight non-heat-acclimated menreceived three experimental treatments (counterbalanced design) immediately after exercise-induced dehydration (33°C) to 4%body weight loss. Treatments were intravenous 0.45% NaCl (iv; 25 ml/kg), no fluid (NF), and oral saline (Oral; 25 ml/kg).After rehydration and rest (2 h total), subjects walked at 50% maximalO2 consumption for up to 90 min at36°C. The following observations were made: 1) heart rate was higher(P < 0.05) in Oral vs. ivat minutes 45, 60, and75 of exercise;2) rectal temperature, sweat rate, percent change in PV, and change in plasma Osmo were similar between ivand Oral; 3) change in plasmanorepinephrine decreased less (P < 0.05) in Oral compared with iv at minute45; 4) changes in plasma adrenocorticotropic hormone and cortisol were similar between ivand Oral after exercise was initiated; and5) exercise time was similar betweeniv (77.4 ± 5.4 min) and Oral (84.2 ± 2.3 min). These datasuggest that after exercise-induced dehydration, iv and Oral wereequally effective as rehydration treatments. Thermoregulation, changein adrenocorticotropic hormone, and change in cortisol were notdifferent between iv and Oral after exercise began; this is likely dueto similar percent change in PV and change in Osmo. 相似文献
9.
Synchronous growth of a freshwater diatom Melosira italica under natural environment 总被引:1,自引:0,他引:1
Summary A filamentous diatom Melosira italica was collected at the beginning of rainy season from a shallow lake in the tropical savanna region in Brazil. Even the sample taken from surface water contained empty cells in high percentages. The number of cells per filament of M. italica showed a peculiar pulse-like frequency distribution with peak values at 4, 8, 12 and 16. Evidences of the synchronous cell division in this planktonic diatom under natural environment are discussed. 相似文献
10.
ngel Ramos-de-Miguel Jos M. Escobar David Greiner Domingo Benítez Eduardo Rodríguez Albert Oliver Marcos Hernndez ngel Ramos-Macías 《PLoS computational biology》2022,18(5)
There is a growing interest in biomedical engineering in developing procedures that provide accurate simulations of the neural response to electrical stimulus produced by implants. Moreover, recent research focuses on models that take into account individual patient characteristics.We present a phenomenological computational model that is customized with the patient’s data provided by the electrically evoked compound action potential (ECAP) for simulating the neural response to electrical stimulus produced by the electrodes of cochlear implants (CIs). The model links the input currents of the electrodes to the simulated ECAP.Potentials and currents are calculated by solving the quasi-static approximation of the Maxwell equations with the finite element method (FEM). In ECAPs recording, an active electrode generates a current that elicits action potentials in the surrounding auditory nerve fibers (ANFs). The sum of these action potentials is registered by other nearby electrode. Our computational model emulates this phenomenon introducing a set of line current sources replacing the ANFs by a set of virtual neurons (VNs). To fit the ECAP amplitudes we assign a suitable weight to each VN related with the probability of an ANF to be excited. This probability is expressed by a cumulative beta distribution parameterized by two shape parameters that are calculated by means of a differential evolution algorithm (DE). Being the weights function of the current density, any change in the design of the CI affecting the current density produces changes in the weights and, therefore, in the simulated ECAP, which confers to our model a predictive capacity.The results of the validation with ECAP data from two patients are presented, achieving a satisfactory fit of the experimental data with those provided by the proposed computational model. 相似文献