全文获取类型
收费全文 | 3480篇 |
免费 | 234篇 |
专业分类
3714篇 |
出版年
2024年 | 3篇 |
2023年 | 42篇 |
2022年 | 64篇 |
2021年 | 130篇 |
2020年 | 97篇 |
2019年 | 129篇 |
2018年 | 134篇 |
2017年 | 108篇 |
2016年 | 194篇 |
2015年 | 238篇 |
2014年 | 228篇 |
2013年 | 257篇 |
2012年 | 303篇 |
2011年 | 296篇 |
2010年 | 208篇 |
2009年 | 165篇 |
2008年 | 194篇 |
2007年 | 163篇 |
2006年 | 168篇 |
2005年 | 128篇 |
2004年 | 118篇 |
2003年 | 95篇 |
2002年 | 64篇 |
2001年 | 29篇 |
2000年 | 20篇 |
1999年 | 15篇 |
1998年 | 22篇 |
1997年 | 4篇 |
1996年 | 6篇 |
1995年 | 10篇 |
1994年 | 11篇 |
1993年 | 5篇 |
1992年 | 8篇 |
1991年 | 7篇 |
1990年 | 2篇 |
1989年 | 6篇 |
1988年 | 6篇 |
1987年 | 7篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 4篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1970年 | 1篇 |
排序方式: 共有3714条查询结果,搜索用时 15 毫秒
921.
922.
Epidemiology,genetic diversity,and evolution of endemic feline immunodeficiency virus in a population of wild cougars
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Biek R Rodrigo AG Holley D Drummond A Anderson CR Ross HA Poss M 《Journal of virology》2003,77(17):9578-9589
Within the large body of research on retroviruses, the distribution and evolution of endemic retroviruses in natural host populations have so far received little attention. In this study, the epidemiology, genetic diversity, and molecular evolution of feline immunodeficiency virus specific to cougars (FIVpco) was examined using blood samples collected over several years from a free-ranging cougar population in the western United States. The virus prevalence was 58% in this population (n = 52) and increased significantly with host age. Based on phylogenetic analysis of fragments of envelope (env) and polymerase (pol) genes, two genetically distinct lineages of FIVpco were found to cooccur in the population but not in the same individuals. Within each of the virus lineages, geographically nearby isolates formed monophyletic clusters of closely related viruses. Sequence diversity for env within a host rarely exceeded 1%, and the evolution of this gene was dominated by purifying selection. For both pol and env, our data indicate mean rates of molecular evolution of 1 to 3% per 10 years. These results support the premise that FIVpco is well adapted to its cougar host and provide a basis for comparing lentivirus evolution in endemic and epidemic infections in natural hosts. 相似文献
923.
Glutamine synthetase activity and glutamine content in brain: modulation by NMDA receptors and nitric oxide 总被引:18,自引:0,他引:18
Kosenko E Llansola M Montoliu C Monfort P Rodrigo R Hernandez-Viadel M Erceg S Sánchez-Perez AM Felipo V 《Neurochemistry international》2003,43(4-5):493-499
Acute intoxication with large doses of ammonia leads to rapid death. The main mechanism for ammonia elimination in brain is its reaction with glutamate to form glutamine. This reaction is catalyzed by glutamine synthetase and consumes ATP. In the course of studies on the molecular mechanism of acute ammonia toxicity, we have found that glutamine synthetase activity and glutamine content in brain are modulated by NMDA receptors and nitric oxide. The main findings can be summarized as follows.Blocking NMDA receptors prevents ammonia-induced depletion of brain ATP and death of rats but not the increase in brain glutamine, indicating that ammonia toxicity is not due to increased activity of glutamine synthetase or formation of glutamine but to excessive activation of NMDA receptors.Blocking NMDA receptors in vivo increases glutamine synthetase activity and glutamine content in brain, indicating that tonic activation of NMDA receptors maintains a tonic inhibition of glutamine synthetase.Blocking NMDA receptors in vivo increases the activity of glutamine synthetase assayed in vitro, indicating that increased activity is due to a covalent modification of the enzyme. Nitric oxide inhibits glutamine synthetase, indicating that the covalent modification that inhibits glutamine synthetase is a nitrosylation or a nitration.Inhibition of nitric oxide synthase increases the activity of glutamine synthetase, indicating that the covalent modification is reversible and it must be an enzyme that denitrosylate or denitrate glutamine synthetase.NMDA mediated activation of nitric oxide synthase is responsible only for part of the tonic inhibition of glutamine synthetase. Other sources of nitric oxide are also contributing to this tonic inhibition.Glutamine synthetase is not working at maximum rate in brain and its activity may be increased pharmacologically by manipulating NMDA receptors or nitric oxide content. This may be useful, for example, to increase ammonia detoxification in brain in hyperammonemic situations. 相似文献
924.
925.
Polarimetry is used for continuous online monitoring of optical resolution by preferential crystallization. In combination with refractometry the liquid phase composition is determined, allowing one to follow the resolution progress quantitatively. The measurement techniques were calibrated up to relatively high solution concentrations and combined with the crystallizer. The resolution of DL-threonine was performed by preferential crystallization experiments in aqueous solution varying several process parameters like supersaturation, seed amount, initial enantiomeric excess, and scale. The resolution progress can be conveniently described by profiles of the optical rotation (polarimetric signal) and the crystallization pathway in the corresponding ternary phase diagram. The method outlined is applicable for dynamic process optimization and control purposes in "quasi-continuous" chiral separation processes. 相似文献
926.
927.
Machado-Vieira R Schmidt AP Avila TT Kapczinski F Soares JC Souza DO Portela LV 《Life sciences》2004,76(7):805-811
Bipolar disorder is a chronic and severe mental disorder. Recently, new animal models have emerged to further investigate underlying mechanisms of bipolar disorder such as ouabain-induced hyperactivity in rats. In this study, we investigated the cerebrospinal fluid levels of S100B protein as a putative marker of astrocytic activity in bipolar mania induced by intracerebroventricular administration of ouabain in rats. Ouabain induced a two-fold increase in crossing responses in the open field test and increased 30% the cerebrospinal fluid concentration of S100B, as compared to vehicle group. Our findings reinforce the role of astroglial cells in the pathogenesis of bipolar disorder and S100B protein as a marker of bipolar mania. 相似文献
928.
da Silva Gomes RA Batista RP Costa de Almeida A da Fonseca DN Juliano L Hial V 《Analytical biochemistry》2003,316(1):11-14
An intramolecularly quenched fluorogenic peptide containing o-aminobenzoyl (Abz) and ethylenediamine 2,4-dinitrophenyl (Eddnp) groups at amino- and carboxyl-terminal amino acid residues, Abz-Lys-Pro-Ile-Glu-Phe-Phe-Arg-Leu-Eddnp, was hydrolyzed by purified human pepsin, gastricsin, and gastric juice uniquely at the Phe-Phe bond. Kinetic parameters determined for purified pepsin were K(m)=0.68+/-0.11 microM; k(cat)=6.3+/-0.16s(-1); k(cat)/K(m)=9.26s(-1) microM(-1); Gastricsin showed K(m)=2.69+/-0.18 microM; k(cat)=0.03+/-0.005s(-1); k(cat)/K(m)=0.011s(-1) microM(-1). Gastric juice (21 samples) from subjects without gastric disorders at endoscopy examination showed activities varying from 0.0008 to 9.72 micromolml(-1)min(-1). Pepstatin A inhibition of gastric juice enzymatic activity was complete at 3.4x10(-5)M (final concentration) inhibitor. In the proposed method the presence of a unique scissile bond in the synthetic substrate provides a direct ratio between enzymatic activity and amount of substrate hydrolyzed, and a unique step reaction facilitates the use of this assay for the determination of the activity of aspartic proteinases in biological fluids and during enzyme purification procedures. 相似文献
929.
Yang H Cooley D Legakis JE Ge Q Andrade R Mattingly RR 《The Journal of biological chemistry》2003,278(15):13278-13285
The Ras-GRF1 exchange factor, which is regulated by increases in intracellular calcium and the release of G beta gamma subunits from heterotrimeric G proteins, plays a critical role in the activation of neuronal Ras. Activation of G protein-coupled receptors stimulates an increase in the phosphorylation of Ras-GRF1 at certain serine residues. The first of these sites to be identified, Ser(916) in the mouse sequence (equivalent to Ser(898) in the rat sequence), is required for full activation of the Ras exchange factor activity of Ras-GRF1 by muscarinic receptors. We demonstrate here that Ras-GRF1 is highly expressed in rat brain compared with the Sos exchange factor and that there is an increase in incorporation of (32)P into Ser(898) of brain Ras-GRF1 following activation of protein kinase A. Phosphorylation of Ras-GRF1 at Ser(916) is also required for maximal induction of Ras-dependent neurite outgrowth in PC12 cells. A novel antibody (termed 2152) that selectively recognizes Ras-GRF1 when it is phosphorylated at Ser(916/898) confirmed the regulated phosphorylation of Ras-GRF1 by Western blotting in both model systems of transfected COS-7 and PC12 cells and also of the endogenous protein in rat forebrain slices. Indirect confocal immunofluorescence of transfected PC12 cells using antibody 2152 demonstrated reactivity only under conditions in which Ras-GRF1 was phosphorylated at Ser(916/898). Confocal immunofluorescence of cortical slices of rat brain revealed widespread and selective phosphorylation of Ras-GRF1 at Ser(898). In the prefrontal cortex, there was striking phosphorylation of Ras-GRF1 in the dendritic tree, supporting a role for Ras activation and signal transduction in neurotransmission in this area. 相似文献
930.
Murillo R Lasa R Goulson D Williams T Muñoz D Caballero P 《Journal of economic entomology》2003,96(6):1668-1674
The influence of an optical brightener, Tinopal LPW, on the activity of a purified genotype of the nucleopolyhedrovirus (SeMNPV) of the beet armyworm, Spodoptera exigua (Hübner), was determined in second to fifth instar (L2-L5) S. exigua. When mixed with viral occlusion bodies (OB) 1% Tinopal LPW significantly reduced the median lethal dose (LD50) of the virus in all instars compared with insects treated with SeMNPV alone. Levels of enhancement, as determined by LD50 values, ranged from 2.6- to 580-fold, depending on the instar. The greatest enhancement occurred on the two later instars, L4 (70-fold) and L5 (580-fold), which show a much higher resistance to SeMNPV infection than earlier instars. The median time to death (MTD) values were not significantly different in any instar among larvae treated with SeMNPV + Tinopal LPW and those treated with SeMNPV alone. Larval development in SeMNPV + Tinopal LPW treated larvae was retarded, in second and fourth instars, compared with controls or larvae treated with SeMNPV alone. The OB yields from SeMNPV treated larvae were almost 1.6-fold greater in second instars (9.3 x 10(6) OBs/larvae), and 1.9-fold greater in fourth instars (1.9 x 10(8) OBs/larvae), than those obtained in larvae treated with SeMNPV + Tinopal LPW. The addition of 1% Tinopal LPW to the virus suspension did not alter the genotypic composition of viral progeny during four successive passages of the virus. 相似文献