全文获取类型
收费全文 | 593篇 |
免费 | 34篇 |
国内免费 | 1篇 |
出版年
2024年 | 2篇 |
2022年 | 6篇 |
2021年 | 18篇 |
2020年 | 8篇 |
2019年 | 12篇 |
2018年 | 15篇 |
2017年 | 9篇 |
2016年 | 24篇 |
2015年 | 28篇 |
2014年 | 37篇 |
2013年 | 47篇 |
2012年 | 45篇 |
2011年 | 56篇 |
2010年 | 28篇 |
2009年 | 27篇 |
2008年 | 44篇 |
2007年 | 29篇 |
2006年 | 31篇 |
2005年 | 16篇 |
2004年 | 31篇 |
2003年 | 21篇 |
2002年 | 17篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 4篇 |
1998年 | 2篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1993年 | 2篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1988年 | 2篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 5篇 |
1982年 | 4篇 |
1981年 | 5篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1977年 | 2篇 |
1976年 | 5篇 |
1975年 | 2篇 |
1970年 | 2篇 |
1956年 | 1篇 |
1955年 | 1篇 |
1953年 | 2篇 |
1952年 | 1篇 |
1950年 | 1篇 |
1945年 | 1篇 |
1935年 | 1篇 |
排序方式: 共有628条查询结果,搜索用时 15 毫秒
111.
112.
Samuel K. Buxton Claude L. Charvet Cedric Neveu Jacques Cabaret Jacques Cortet Nicolas Peineau Melanie Abongwa Elise Courtot Alan P. Robertson Richard J. Martin 《PLoS pathogens》2014,10(1)
Nicotinic acetylcholine receptors (nAChRs) of parasitic nematodes are required for body movement and are targets of important “classical” anthelmintics like levamisole and pyrantel, as well as “novel” anthelmintics like tribendimidine and derquantel. Four biophysical subtypes of nAChR have been observed electrophysiologically in body muscle of the nematode parasite Oesophagostomum dentatum, but their molecular basis was not understood. Additionally, loss of one of these subtypes (G 35 pS) was found to be associated with levamisole resistance. In the present study, we identified and expressed in Xenopus oocytes, four O. dentatum nAChR subunit genes, Ode-unc-38, Ode-unc-63, Ode-unc-29 and Ode-acr-8, to explore the origin of the receptor diversity. When different combinations of subunits were injected in Xenopus oocytes, we reconstituted and characterized four pharmacologically different types of nAChRs with different sensitivities to the cholinergic anthelmintics. Moreover, we demonstrate that the receptor diversity may be affected by the stoichiometric arrangement of the subunits. We show, for the first time, different combinations of subunits from a parasitic nematode that make up receptors sensitive to tribendimidine and derquantel. In addition, we report that the recombinant levamisole-sensitive receptor made up of Ode-UNC-29, Ode-UNC-63, Ode-UNC-38 and Ode-ACR-8 subunits has the same single-channel conductance, 35 pS and 2.4 ms mean open-time properties, as the levamisole-AChR (G35) subtype previously identified in vivo. These data highlight the flexible arrangements of the receptor subunits and their effects on sensitivity and resistance to the cholinergic anthelmintics; pyrantel, tribendimidine and/or derquantel may still be effective on levamisole-resistant worms. 相似文献
113.
Cedric Annweiler Olivier Beauchet Robert Bartha Vladimir Hachinski Manuel Montero-Odasso 《PloS one》2014,9(1)
Background
Vitamin D is involved in brain physiology and lower-extremity function. We investigated spectroscopy in a cohort of older adults to explore the hypothesis that lower vitamin D status was associated with impaired neuronal function in caudal primary motor cortex (cPMC) measured by proton magnetic resonance spectroscopic imaging.Methods
Twenty Caucasian community-dwellers (mean±standard deviation, 74.6±6.2 years; 35.0% female) from the ‘Gait and Brain Study’ were included in this analysis. Ratio of N-acetyl-aspartate to creatine (NAA/Cr), a marker of neuronal function, was calculated in cPMC. Participants were categorized according to mean NAA/Cr. Lower vitamin D status was defined as serum 25-hydroxyvitamin D (25OHD) concentration <75 nmol/L. Age, gender, number of comorbidities, vascular risk, cognition, gait performance, vitamin D supplements, undernourishment, cPMC thickness, white matter hyperintensities grade, serum parathyroid hormone concentration, and season of evaluation were used as potential confounders.Results
Compared to participants with high NAA/Cr (n = 11), those with low NAA/Cr (i.e., reduced neuronal function) had lower serum 25OHD concentration (P = 0.044) and more frequently lower vitamin D status (P = 0.038). Lower vitamin D status was cross-sectionally associated with a decrease in NAA/Cr after adjustment for clinical characteristics (β = −0.41, P = 0.047), neuroimaging measures (β = −0.47, P = 0.032) and serum measures (β = −0.45, P = 0.046).Conclusions
Lower vitamin D status was associated with reduced neuronal function in cPMC. These novel findings need to be replicated in larger and preferably longitudinal cohorts. They contribute to explain the pathophysiology of gait disorders in older adults with lower vitamin D status, and provide a scientific base for vitamin D replacement trials. 相似文献114.
Monika L. Bayer Peter Schjerling Andreas Herchenhan Cedric Zeltz Katja M. Heinemeier Lise Christensen Michael Krogsgaard Donald Gullberg Michael Kjaer 《PloS one》2014,9(1)
Mechanical loading of tendon cells results in an upregulation of mechanotransduction signaling pathways, cell-matrix adhesion and collagen synthesis, but whether unloading removes these responses is unclear. We investigated the response to tension release, with regard to matrix proteins, pro-inflammatory mediators and tendon phenotypic specific molecules, in an in vitro model where tendon-like tissue was engineered from human tendon cells. Tissue sampling was performed 1, 2, 4 and 6 days after surgical de-tensioning of the tendon construct. When tensile stimulus was removed, integrin type collagen receptors showed a contrasting response with a clear drop in integrin subunit α11 mRNA and protein expression, and an increase in α2 integrin mRNA and protein levels. Further, specific markers for tendon cell differentiation declined and normal tendon architecture was disturbed, whereas pro-inflammatory molecules were upregulated. Stimulation with the cytokine TGF-β1 had distinct effects on some tendon-related genes in both tensioned and de-tensioned tissue. These findings indicate an important role of mechanical loading for cellular and matrix responses in tendon, including that loss of tension leads to a decrease in phenotypical markers for tendon, while expression of pro-inflammatory mediators is induced. 相似文献
115.
Rachid Rezgui Roxane Lestini Jo?lle Kühn Xenia Fave Lauren McLeod Hannu Myllykallio Antigoni Alexandrou Cedric Bouzigues 《PloS one》2014,9(11)
As DNA repair enzymes are essential for preserving genome integrity, understanding their substrate interaction dynamics and the regulation of their catalytic mechanisms is crucial. Using single-molecule imaging, we investigated the association and dissociation kinetics of the bipolar endonuclease NucS from Pyrococcus abyssi (Pab) on 5′ and 3′-flap structures under various experimental conditions. We show that association of the PabNucS with ssDNA flaps is largely controlled by diffusion in the NucS-DNA energy landscape and does not require a free 5′ or 3′ extremity. On the other hand, NucS dissociation is independent of the flap length and thus independent of sliding on the single-stranded portion of the flapped DNA substrates. Our kinetic measurements have revealed previously unnoticed asymmetry in dissociation kinetics from these substrates that is markedly modulated by the replication clamp PCNA. We propose that the replication clamp PCNA enhances the cleavage specificity of NucS proteins by accelerating NucS loading at the ssDNA/dsDNA junctions and by minimizing the nuclease interaction time with its DNA substrate. Our data are also consistent with marked reorganization of ssDNA and nuclease domains occurring during NucS catalysis, and indicate that NucS binds its substrate directly at the ssDNA-dsDNA junction and then threads the ssDNA extremity into the catalytic site. The powerful techniques used here for probing the dynamics of DNA-enzyme binding at the single-molecule have provided new insight regarding substrate specificity of NucS nucleases. 相似文献
116.
117.
Cedric Moro Isabelle Harant Pierre-Marie Badin François-Xavier Patarca Jean-Claude Guilland Virginie Bourlier Dominique Langin Isabelle De Glisezinski 《Journal of physiology and biochemistry》2014,70(2):583-591
The aim of the present study was to investigate the influence of substrate availability on fuel selection during exercise. Eight endurance-trained male cyclists performed 90-min exercise at 70 % of their maximal oxygen uptake in a cross-over design, either in rested condition (CON) or the day after 2-h exercise practised at 70 % of maximal oxygen uptake (EX). Subjects were given a sucrose load (0.75 g kg?1 body weight) 45 min after the beginning of the 90-min exercise test. Lipolysis was measured in subcutaneous abdominal adipose tissue (SCAT) by microdialysis and substrate oxidation by indirect calorimetry. Lipid oxidation increased during exercise and tended to decrease during sucrose ingestion in both conditions. Lipid oxidation was higher during the whole experimental period in the EX group (p?=?0.004). Interestingly, fuel selection, assessed by the change in respiratory exchange ratio (RER), was increased in the EX session (p?=?0.002). This was paralleled by a higher rate of SCAT lipolysis reflected by dialysate glycerol, plasma glycerol, and fatty acids (FA) levels (p?<?0.001). Of note, we observed a significant relationship between whole-body fat oxidation and dialysate glycerol in both sessions (r 2?=?0.33, p?=?0.02). In conclusion, this study highlights the limiting role of lipolysis and plasma FA availability to whole-body fat oxidation during exercise in endurance-trained subjects. This study shows that adipose tissue lipolysis is a determinant of fuel selection during exercise in healthy subjects. 相似文献
118.
H. Ranjith W. Dharmaratne Cedric Shackleton Esther Roitman Eliahu Caspi 《The Journal of steroid biochemistry and molecular biology》1993,45(6):571-580
Treatment of 19-[oxygenated]-androst-4-ene-3,17-dione with Mn(AcO)3 and ClCH2COOH in benzene gave epimeric mixtures of the corresponding 2ξ-chloroacetates and 2ξ-acetates. The products were processed to give the title compound. For the synthesis of the 2-18O analog, ClCH2C18OOH was used, which was prepared from ClCH2COCl. 相似文献
119.
120.