全文获取类型
收费全文 | 3509篇 |
免费 | 210篇 |
国内免费 | 5篇 |
出版年
2023年 | 25篇 |
2022年 | 58篇 |
2021年 | 129篇 |
2020年 | 69篇 |
2019年 | 88篇 |
2018年 | 93篇 |
2017年 | 72篇 |
2016年 | 119篇 |
2015年 | 147篇 |
2014年 | 216篇 |
2013年 | 272篇 |
2012年 | 296篇 |
2011年 | 278篇 |
2010年 | 228篇 |
2009年 | 160篇 |
2008年 | 162篇 |
2007年 | 170篇 |
2006年 | 147篇 |
2005年 | 146篇 |
2004年 | 95篇 |
2003年 | 108篇 |
2002年 | 98篇 |
2001年 | 40篇 |
2000年 | 51篇 |
1999年 | 35篇 |
1998年 | 28篇 |
1997年 | 17篇 |
1996年 | 12篇 |
1995年 | 21篇 |
1993年 | 11篇 |
1992年 | 24篇 |
1991年 | 10篇 |
1990年 | 12篇 |
1989年 | 17篇 |
1988年 | 17篇 |
1986年 | 20篇 |
1985年 | 22篇 |
1984年 | 12篇 |
1983年 | 9篇 |
1982年 | 12篇 |
1981年 | 10篇 |
1980年 | 12篇 |
1979年 | 13篇 |
1978年 | 18篇 |
1976年 | 9篇 |
1975年 | 8篇 |
1973年 | 13篇 |
1972年 | 9篇 |
1971年 | 10篇 |
1969年 | 8篇 |
排序方式: 共有3724条查询结果,搜索用时 31 毫秒
991.
Re-evaluation of how artemisinins work in light of emerging evidence of in vitro resistance 总被引:5,自引:0,他引:5
Krishna S Woodrow CJ Staines HM Haynes RK Mercereau-Puijalon O 《Trends in molecular medicine》2006,12(5):200-205
There are more than half a billion cases of malaria every year. Combinations of an artemisinin with other antimalarial drugs are now recommended treatments for Plasmodium falciparum malaria in most endemic areas. These treatment regimens act rapidly to relieve symptoms and effect cure. There is considerable controversy on how artemisinins work and over emerging indications of resistance to this class of antimalarial drugs. Several individual molecules have been proposed as targets for artemisinins, in addition to the idea that artemisinins might have many targets at the same time. Our suggestion that artemisinins inhibit the parasite-encoded sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) PfATP6 has gained support from recent observations that a polymorphism in the gene encoding PfATP6 is associated with in vitro resistance to artemether in field isolates of P. falciparum. 相似文献
992.
Kolluru GK Tamilarasan KP Geetha Priya S Durgha NP Chatterjee S 《Cell biology international》2006,30(5):427-438
Recent advances in cadmium toxicity research suggest an association between cadmium and vascular diseases. However, the mechanisms of cadmium implications in vascular diseases are not yet explained. The objective of our present study is to explore the mechanism of cadmium induced endothelial dysfunction. Doses of 0, 1 and 5microM cadmium chloride were used to test the effects of cadmium on nitric oxide induced tube formation, cellular migration and subcellular actin polymerization in ECV-304 endothelial cells. An egg-yolk vascular bed model was used to study the effects of cadmium on angiogenesis. Results of the present study show that 5microM cadmium chloride effectively inhibited angiogenesis, cellular migration and tube formation. Phalloidin staining, which represents actin polymerization of endothelial cells, reveals that cadmium induces an altered F-actin pattern, which could be the prime cause for cadmium mediated inhibition of cellular migration and angiogenesis. Cadmium was also found to inhibit nitric oxide production in endothelial cells in a calcium free medium, which further hints that cadmium might impair endothelial functions by inhibiting endothelial nitric oxide synthase. 相似文献
993.
Markowitz VM Ivanova N Palaniappan K Szeto E Korzeniewski F Lykidis A Anderson I Mavromatis K Mavrommatis K Kunin V Garcia Martin H Dubchak I Hugenholtz P Kyrpides NC 《Bioinformatics (Oxford, England)》2006,22(14):e359-e367
The application of shotgun sequencing to environmental samples has revealed a new universe of microbial community genomes (metagenomes) involving previously uncultured organisms. Metagenome analysis, which is expected to provide a comprehensive picture of the gene functions and metabolic capacity for microbial communities, needs to be conducted in the context of a comprehensive data management and analysis system. We present in this paper IMG/M, an experimental metagenome data management and analysis system that is based on the Integrated Microbial Genomes (IMG) system. IMG/M provides tools and viewers for analyzing both metagenomes and isolate genomes individually or in a comparative context. IMG/M is available at http://img.jgi.doe.gov/m. 相似文献
994.
Johnson Inbaraj J Krishna MC Gandhidasan R Murugesan R 《Biochimica et biophysica acta》1999,1472(3):462-470
Two naturally occurring anthraquinones, barleriaquinone-I (BQ-I) and barleriaquinone-II (BQ-II), extracted from Barleria buxifolia, are tested for their cytotoxic action by aerobic incubation with human breast adenocarcinoma cells (MCF7). Cytotoxicities, measured as LD(50) (50% inhibition of colony formation) values, show BQ-II to be more active than BQ-I. Electron paramagnetic resonance studies confirm that BQ-II is reductively activated by NADH:cytochrome c reductase to superoxide anion radical. Cyclic voltammetric studies show one quasi-reversible redox couple for both BQ-I and BQ-II. Also, aerobic solutions of both BQ-I and BQ-II on visible illumination generate reactive oxygen species. Formation of O*-2 is studied by both EPR spin trapping and SOD-inhibitable cytochrome c reduction techniques. BQ-I generates more singlet oxygen as evidenced from the photobleaching of N,N-dimethyl-4-nitrosoaniline. 相似文献
995.
Syamantak Majumder K P Tamilarasan Gopi Krishna Kolluru Ajit Muley C Madhavan Nair Athira Omanakuttan K V G K Murty Suvro Chatterjee 《Biochimie et biologie cellulaire》2007,85(6):709-720
Hepatic stellate cells are liver-specific pericytes and exist in close proximity with endothelial cells. The activation of liver pericytes is intrinsic to liver pathogenesis, and leads to endothelial dysfunction, including the low bioavailability of nitric oxide (NO). However, the role of nitric oxide in pericyte-endothelium cross-talk has not yet been elucidated. This work examines the cellular mechanism of action of NO in pericyte-mediated endothelial dysfunction. We used in vitro coculture and conditioned medium systems to study the effects of activated liver pericytes on endothelial function, and an egg yolk vascular bed model was used to study the effects of activated pericytes on angiogenesis. This study also demonstrates that activated pericytes attenuate the migration, proliferation, permeability, and NO production of endothelial cells. Our results demonstrate that activated pericytes restrict angiogenesis in egg yolk vascular bed models, and NO supplementation recovers 70% of the inhibition. Our results also demonstrate that supplementation with NO, sildenafil citrate (phosphodiesterase inhibitor), and 8-bromo-cGMP (cGMP analog) partially recovers activated-pericyte-mediated endothelium dysfunction. We conclude that NO-cGMP alleviates activated-pericyte-associated endothelial dysfunction, including angiogenesis, in a cGMP-dependent manner. 相似文献
996.
Inhibition of hexose transport and abrogation of pH homeostasis in the intraerythrocytic malaria parasite by an O-3-hexose derivative 总被引:1,自引:0,他引:1
An O-3-hexose derivative, shown previously to inhibit a malaria parasite hexose transporter expressed in Xenopus oocytes as well as to suppress the multiplication of parasites, both in vitro and in vivo, was shown here to block the uptake of hexose sugars into isolated blood-stage parasites. This led to a decline in ATP levels and the loss of intracellular pH control. The results are consistent with those obtained with the cloned transporter. They support the notion that the transporter mediates uptake of glucose into the intraerythrocytic parasite and provide further support for the view that it is a suitable antimalarial drug target. 相似文献
997.
Administration of precocene II (6,7-dimethoxy-2, 2-dimethyl chromene) to freshly emerged virgin female flies of S. ruficornis adversely affected the development and differentiation of ovarian follicles leading to a number of morphological abnormalities. Precocene treatment resulted into suppression of development of egg chamber, differentiation of follicular epithelium, degeneration of nurse cells, growth of oocyte and uptake of yolk granules by oocytes. The results suggest that precocene induced effects are due to deficiency of juvenile hormone. 相似文献
998.
Ligand selectivity and affinity of chemokine receptor CXCR1. Role of N-terminal domain 总被引:2,自引:0,他引:2
Glu-Leu-Arg ("ELR") CXC chemokines interleukin-8 (IL-8) and melanoma growth stimulatory activity (MGSA) recruit neutrophils by binding and activating two receptors, CXCR1 and CXCR2. CXCR1 is specific, binding only IL-8 with nanomolar affinity, whereas CXCR2 is promiscuous, binding all ELRCXC chemokines with high affinity. Receptor signaling consists of two events: interactions between the ligand N-terminal loop (N-loop) and receptor N-terminal domain (N-domain) residues (site I), and between the ligand N-terminal ELR and the receptor juxtamembrane domain (J-domain) residues (site II). It is not known how these interactions mediate ligand affinity and selectivity, and whether binding at one site influences binding and function at the other. Sequence analysis and structure-function studies have suggested that the receptor N-domain plays an important role in ligand selectivity. Here, we report ligand-binding properties and structural characteristics of the CXCR1 N-domain in solution and in detergent micelles that mimic the native membrane environment. We find that IL-8 binds the N-domain with significantly higher affinity in micelles than in solution (approximately 1 microM versus approximately 20 microM) and that MGSA does not bind the N-domain in solution but does in micelles with appreciable affinity (approximately 3 microM). We find that the N-domain is structured in micelles and that the entire N-domain interacts with the micelle in an extended fashion. We conclude that the micellar environment constrains the N-domain, and this conformational restraint influences its ligand-binding properties. Most importantly, our data suggest that for both ligands, site I interaction provides similar affinity and that differential coupling between site I and II interactions is responsible for the observed differences in affinity. 相似文献
999.
1000.