全文获取类型
收费全文 | 18793篇 |
免费 | 1402篇 |
国内免费 | 2篇 |
专业分类
20197篇 |
出版年
2022年 | 74篇 |
2021年 | 167篇 |
2020年 | 131篇 |
2019年 | 140篇 |
2018年 | 285篇 |
2017年 | 250篇 |
2016年 | 444篇 |
2015年 | 797篇 |
2014年 | 734篇 |
2013年 | 1058篇 |
2012年 | 1272篇 |
2011年 | 1263篇 |
2010年 | 752篇 |
2009年 | 627篇 |
2008年 | 1121篇 |
2007年 | 1100篇 |
2006年 | 1071篇 |
2005年 | 1020篇 |
2004年 | 960篇 |
2003年 | 889篇 |
2002年 | 808篇 |
2001年 | 422篇 |
2000年 | 436篇 |
1999年 | 397篇 |
1998年 | 181篇 |
1997年 | 156篇 |
1996年 | 138篇 |
1995年 | 143篇 |
1994年 | 129篇 |
1993年 | 105篇 |
1992年 | 235篇 |
1991年 | 230篇 |
1990年 | 210篇 |
1989年 | 164篇 |
1988年 | 181篇 |
1987年 | 151篇 |
1986年 | 140篇 |
1985年 | 126篇 |
1984年 | 118篇 |
1983年 | 94篇 |
1982年 | 88篇 |
1981年 | 110篇 |
1980年 | 83篇 |
1979年 | 111篇 |
1978年 | 107篇 |
1977年 | 83篇 |
1976年 | 93篇 |
1975年 | 78篇 |
1974年 | 89篇 |
1971年 | 80篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Rousseau D Héliès-Toussaint C Moreau D Raederstorff D Grynberg A 《American journal of physiology. Heart and circulatory physiology》2003,285(3):H1294-H1302
The cardiovascular consequences of eicosapentaenoic acid (EPA)- and docosahexaenoic acid (DHA)-specific intake were evaluated in vivo in a hyperinsulinemia (HI) model induced by dietary fructose intake. Wistar rats were fed a diet containing (or not for control) either EPA or DHA. The rise in blood pressure (BP), heart rate, and ECG were continuously monitored using an intra-abdominal telemetry system. The myocardial phospholipid fatty acid profile was significantly affected by DHA intake but less by EPA intake. The data indicated a reduced rise in BP in both DHA and EPA HI groups compared with controls. This result was confirmed by tail-cuff measurement after 5 wk [133.3 +/- 1.67 and 142.5 +/- 1.12 mmHg in n-3 polyunsaturated fatty acid (PUFA) and control groups, respectively], whereas n-3 PUFA did not affect BP in non-HI rats (116.3 +/- 3.33 mmHg). The heart rate was lower in the HI DHA group than in the other two dietary HI groups. Moreover, DHA induced a significantly shorter QT interval. It is concluded that the cardioactive component of fish oils is DHA through a mechanism that may involve the cardiac adrenergic system. 相似文献
992.
Hilgert M Hartmann J Löffelholz K Jeltsch H Cassel JC Klein J 《Neurochemical research》2003,28(3-4):467-472
The cholinergic inputs to the rat hippocampus were lesioned by intraseptal injections of 192 IgG-saporin. After 15 days, fetal septal cells were grafted into the hippocampus. Thirteen months later, hippocampal acetylcholine (ACh) release was studied by microdialysis. Lesioning reduced basal ACh release (100%) to 20% of normal, which was compensated for by the graft (71%). Infusion of the serotonin uptake inhibitor citalopram (100 M) enhanced ACh release to the same extent (% of basal release) in all rat groups. Systemic injection of 8-OH-DPAT (0.5 mg/kg, SC), an agonist of 5-HT1A receptors, caused a smaller ACh release than citalopram. Acetylcholinesterase (AChE) staining and densitometric quantification revealed that the lesion-induced reduction of the AChE-staining density was compensated for by septal grafting. In conclusion, both histochemical and biochemical methods showed that cholinergic hippocampal parameters were drastically impaired by 192 IgG-saporin lesions, but were almost completely restored by septal grafting. The graft responded to intrinsic serotonergic regulation. 相似文献
993.
994.
Motions and structural variability within toxins: implication for their use as scaffolds for protein engineering 下载免费PDF全文
Gilquin B Bourgoin M Ménez R Le Du MH Servent D Zinn-Justin S Ménez A 《Protein science : a publication of the Protein Society》2003,12(2):266-277
Animal toxins are small proteins built on the basis of a few disulfide bonded frameworks. Because of their high variability in sequence and biologic function, these proteins are now used as templates for protein engineering. Here we report the extensive characterization of the structure and dynamics of two toxin folds, the "three-finger" fold and the short alpha/beta scorpion fold found in snake and scorpion venoms, respectively. These two folds have a very different architecture; the short alpha/beta scorpion fold is highly compact, whereas the "three-finger" fold is a beta structure presenting large flexible loops. First, the crystal structure of the snake toxin alpha was solved at 1.8-A resolution. Then, long molecular dynamics simulations (10 ns) in water boxes of the snake toxin alpha and the scorpion charybdotoxin were performed, starting either from the crystal or the solution structure. For both proteins, the crystal structure is stabilized by more hydrogen bonds than the solution structure, and the trajectory starting from the X-ray structure is more stable than the trajectory started from the NMR structure. The trajectories started from the X-ray structure are in agreement with the experimental NMR and X-ray data about the protein dynamics. Both proteins exhibit fast motions with an amplitude correlated to their secondary structure. In contrast, slower motions are essentially only observed in toxin alpha. The regions submitted to rare motions during the simulations are those that exhibit millisecond time-scale motions. Lastly, the structural variations within each fold family are described. The localization and the amplitude of these variations suggest that the regions presenting large-scale motions should be those tolerant to large insertions or deletions. 相似文献
995.
Recent habitat fragmentation caused by major roads leads to reduction of gene flow and loss of genetic variability in ground beetles 总被引:16,自引:0,他引:16
Although habitat fragmentation is suspected to jeopardize the long-term survival of many species, few data are available on its impact on the genetic variability of invertebrates. We assess the genetic population structure of the flightless ground beetle Carabus violaceus L., 1758 in a Swiss forest, which is divided into several fragments by a highway and two main roads. Eight samples were collected from different forest fragments and analysed at six microsatellite loci. The largest genetic differentiation was observed between samples separated by roads and in particular by the highway. The number of roads between sites explained 44% of the variance in pairwise F(ST) estimates, whereas the age of the road and the geographical distance between locations were not significant factors. Furthermore, a comparison of allelic richness showed that the genetic variability in a small forest fragment isolated by the highway was significantly lower than in the rest of the study area. These findings strongly support the hypothesis that large roads are absolute barriers to gene flow in C. violaceus, which may lead to a loss of genetic variability in fragmented populations. 相似文献
996.
Baymann F Lebrun E Brugna M Schoepp-Cothenet B Giudici-Orticoni MT Nitschke W 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2003,358(1429):267-274
Genome analyses and the resolution of three-dimensional structures have provided evidence in recent years for hitherto unexpected family relationships between redox proteins of very diverse enzymes involved in bioenergetic electron transport. Many of these enzymes appear in fact to be constructed from only a limited set of building blocks. Phylogenetic analysis of selected units from this "redox enzyme construction kit" indicates an origin for several prominent bioenergetic enzymes that is very early, lying before the divergence of Bacteria and Archaea. Possible scenarios for the early evolution of selected complexes are proposed based on the obtained tree topologies. 相似文献
997.
Karramkam M Hinnen F Berrehouma M Hlavacek C Vaufrey F Halldin C McCarron JA Pike VW Dollé F 《Bioorganic & medicinal chemistry》2003,11(13):2769-2782
In recent years, considerable effort has been spent on the design, synthesis and pharmacological characterization of radiofluorinated derivatives of the 5-HT(1A) receptor antagonist, WAY-100635, for the in vivo study of these receptors in human brain with PET. (Pyridinyl-6)-fluoro- and (pyridinyl-5)-fluoro-analogues of WAY-100635 (6-fluoro and 5-fluoro-WAY-100635, 5a/6a) were synthesized as well as the corresponding chloro-, bromo- and nitro-derivatives as precursors for labelling (5b-d and 6b-d). Comparative radiolabelling of these precursors with fluorine-18 (positron-emitting isotope, 109.8 min half-life) clearly demonstrated that only ortho-fluorination in this pyridine series, and not meta-fluorination, is of interest for the preparation of a radioligand by nucleophilic heteroaromatic substitution. 6-[(18)F]Fluoro-WAY-100635 ([(18)F]5a) can be efficiently synthesized in one step, either from the corresponding 6-bromo precursor (using conventional heating at 145 degrees C for 10 min) or from the corresponding 6-nitro precursor (using microwave activation at 100 W for 1 min). Typically, 15-25 mCi (0.55-0.92 GBq) of 6-[(18)F]fluoro-WAY-100635 ([(18)F]5a, 1-2 Ci/micromol or 37-72 GBq/micromol) were obtained in 50-70 min starting from a 100 mCi (3.7 GBq) aliquot of a batch of cyclotron-produced [(18)F]fluoride. This (18)F-labelled radioligand is now being evaluated in PET studies. 相似文献
998.
Le Diguarher T Ortuno JC Dorey G Shanks D Guilbaud N Pierré A Fauchère JL Hickman JA Tucker GC Casara PJ 《Bioorganic & medicinal chemistry》2003,11(14):3193-3204
A rapid structure-activity study was performed by parallel liquid synthesis on N,N'-disubstitution of 3-amino azepin-2-one to afford potent and specific farnesyl transferase inhibitors with low nM enzymatic and cellular activities. The activities of the selected compounds were validated in vivo, and compounds 41a and 44a presented significant antitumour activity. 相似文献
999.
Abergel C Nitschke W Malarte G Bruschi M Claverie JM Giudici-Orticoni MT 《Structure (London, England : 1993)》2003,11(5):547-555
The study of electron transfer between the copper protein rusticyanin (RCy) and the c(4)-cytochrome CYC(41) of the acidophilic bacterium Acidithiobacillus ferrooxidans has evidenced a remarkable decrease of RCy's redox potential upon complex formation. The structure of the CYC(41) obtained at 2.2 A resolution highlighted a specific glutamate residue (E121) involved in zinc binding as potentially playing a central role in this effect, required for the electron transfer to occur. EPR and stopped-flow experiments confirmed the strong inhibitory effect of divalent cations on CYC(41):RCy complex formation. A docking analysis of the CYC(41) and RCy structure allows us to propose a detailed model for the complex-induced tuning of electron transfer in agreement with our experimental data, which could be representative of other copper proteins involved in electron transfer. 相似文献
1000.