全文获取类型
收费全文 | 1956篇 |
免费 | 138篇 |
国内免费 | 1篇 |
出版年
2023年 | 17篇 |
2022年 | 22篇 |
2021年 | 57篇 |
2020年 | 28篇 |
2019年 | 38篇 |
2018年 | 47篇 |
2017年 | 43篇 |
2016年 | 62篇 |
2015年 | 111篇 |
2014年 | 113篇 |
2013年 | 157篇 |
2012年 | 149篇 |
2011年 | 155篇 |
2010年 | 89篇 |
2009年 | 67篇 |
2008年 | 112篇 |
2007年 | 135篇 |
2006年 | 121篇 |
2005年 | 88篇 |
2004年 | 88篇 |
2003年 | 81篇 |
2002年 | 66篇 |
2001年 | 27篇 |
2000年 | 18篇 |
1999年 | 18篇 |
1998年 | 15篇 |
1997年 | 12篇 |
1996年 | 16篇 |
1995年 | 11篇 |
1994年 | 12篇 |
1993年 | 5篇 |
1992年 | 6篇 |
1991年 | 12篇 |
1990年 | 13篇 |
1989年 | 11篇 |
1988年 | 12篇 |
1987年 | 11篇 |
1986年 | 6篇 |
1985年 | 6篇 |
1984年 | 3篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 2篇 |
1980年 | 4篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 3篇 |
排序方式: 共有2095条查询结果,搜索用时 15 毫秒
991.
A dynamic method (DM) recently proposed for the management of captive subdivided populations was evaluated using the pilot species Drosophila melanogaster. By accounting for the particular genetic population structure, the DM determines the optimal mating pairs, their contributions to progeny and the migration pattern that minimize the overall coancestry in the population with a control of inbreeding levels. After a pre-management period such that one of the four subpopulations had higher inbreeding and differentiation than the others, three management methods were compared for 10 generations over three replicates: (1) isolated subpopulations (IS), (2) one-migrant-per-generation rule (OMPG), (3) DM aimed to produce the same or lower inbreeding coefficient than OMPG. The DM produced the lowest coancestry and equal or lower inbreeding than the OMPG method throughout the experiment. The initially lower fitness and lower variation for nine microsatellite loci of the highly inbred subpopulation were restored more quickly with the DM than with the OMPG method. We provide, therefore, an empirical illustration of the usefulness of the DM as a conservation protocol for captive subdivided populations when pedigree information is available (or can be deduced) and manipulation of breeding pairs is possible. 相似文献
992.
Tania L. Roth 《Hormones and behavior》2011,59(3):315-86
Studies over the past half-century have made it clear that environmental influences in development, particularly stress and traumatic experiences, can remain pervasive across the lifespan. Though it has been hypothesized for some time that the long-term consequences of early-life adversity represent epigenetic influences, it has not been until recently that studies have begun to provide empirical support of experience-driven epigenetic modifications to the genome. Here we focus on this theme, and review current knowledge pertaining to the epigenetics of behavioral development. At the center of our discussion is the brain-derived neurotrophic factor (BDNF) gene, as abnormal BDNF gene activity is a leading etiological hypothesis by which early-life adverse experiences persistently modify brain and behavioral plasticity. 相似文献
993.
Palanisamy Uma Maheswari Manuel Quesada Francesco Buda Anthony L. Spek Jan Reedijk 《Inorganica chimica acta》2011,374(1):406-414
A square-planar compound [Cu(pyrimol)Cl] (pyrimol = 4-methyl-2-N-(2-pyridylmethylene)aminophenolate) abbreviated as CuL-Cl) is described as a biomimetic model of the enzyme galactose oxidase (GOase). This copper(II) compound is capable of stoichiometric aerobic oxidation of activated primary alcohols in acetonitrile/water to the corresponding aldehydes. It can be obtained either from Hpyrimol (HL) or its reduced/hydrogenated form Hpyramol (4-methyl-2-N-(2-pyridylmethyl)aminophenol; H2L) readily converting to pyrimol (L−) on coordination to the copper(II) ion. Crystalline CuL-Cl and its bromide derivative exhibit a perfect square-planar geometry with Cu-O(phenolate) bond lengths of 1.944(2) and 1.938(2) Å. The cyclic voltammogram of CuL-Cl exhibits an irreversible anodic wave at +0.50 and +0.57 V versus ferrocene/ferrocenium (Fc/Fc+) in dry dichloromethane and acetonitrile, respectively, corresponding to oxidation of the phenolate ligand to the corresponding phenoxyl radical. In the strongly donating acetonitrile the oxidation path involves reversible solvent coordination at the Cu(II) centre. The presence of the dominant CuII-L chromophore in the electrochemically and chemically oxidised species is evident from a new fairly intense electronic absorption at 400-480 nm ascribed to a several electronic transitions having a mixed π → π∗(L) intraligand and Cu-Cl → L charge transfer character. The EPR signal of CuL-Cl disappears on oxidation due to strong intramolecular antiferromagnetic exchange coupling between the phenoxyl radical ligand (L) and the copper(II) centre, giving rise to a singlet ground state (S = 0). The key step in the mechanism of the primary alcohol oxidation by CuL-Cl is probably the α-hydrogen abstraction from the equatorially bound alcoholate by the phenoxyl moiety in the oxidised pyrimol ligand, Cu-L, through a five-membered cyclic transition state. 相似文献
994.
Padilla-Morales LF Morales-Pérez CL De La Cruz-Rivera PC Asmar-Rovira G Báez-Pagán CA Quesada O Lasalde-Dominicci JA 《The Journal of membrane biology》2011,243(1-3):47-58
Over the past three decades, the Torpedo californica nicotinic acetylcholine receptor (nAChR) has been one of the most extensively studied membrane protein systems. However, the effects of detergent solubilization on nAChR stability and function are poorly understood. The use of lipid-analog detergents for nAChR solubilization has been shown to preserve receptor stability and functionality. The present study used lipid-analog detergents from phospholipid-analog and cholesterol-analog detergent families for solubilization and affinity purification of the receptor and probed nAChR ion channel function using planar lipid bilayers (PLBs) and stability using analytical size exclusion chromatography (A-SEC) in the detergent-solubilized state. We also examined receptor mobility on the lipidic cubic phase (LCP) by measuring the nAChR mobile fraction and diffusion coefficient through fluorescence recovery after photobleaching (FRAP) experiments using lipid-analog and non-lipid-analog detergents. Our results show that it is possible to isolate stable and functional nAChRs using lipid-analog detergents, with characteristic ion channel currents in PLBs and minimal aggregation as observed in A-SEC. Furthermore, fractional mobility and diffusion coefficient values observed in FRAP experiments were similar to the values observed for these parameters in the recently LCP-crystallized β(2)-adrenergic receptor. The overall results show that phospholipid-analog detergents with 16 carbon acyl-chains support nAChR stability, functionality and LCP mobility. 相似文献
995.
996.
997.
Solomon IH Khatri N Biasini E Massignan T Huettner JE Harris DA 《The Journal of biological chemistry》2011,286(16):14724-14736
There is evidence that alterations in the normal physiological activity of PrP(C) contribute to prion-induced neurotoxicity. This mechanism has been difficult to investigate, however, because the normal function of PrP(C) has remained obscure, and there are no assays available to measure it. We recently reported that cells expressing PrP deleted for residues 105-125 exhibit spontaneous ionic currents and hypersensitivity to certain classes of cationic drugs. Here, we utilize cell culture assays based on these two phenomena to test how changes in PrP sequence and/or cellular localization affect the functional activity of the protein. We report that the toxic activity of Δ105-125 PrP requires localization to the plasma membrane and depends on the presence of a polybasic amino acid segment at the N terminus of PrP. Several different deletions spanning the central region as well as three disease-associated point mutations also confer toxic activity on PrP. The sequence domains identified in our study are also critical for PrP(Sc) formation, suggesting that common structural features may govern both the functional activity of PrP(C) and its conversion to PrP(Sc). 相似文献
998.
Luo H Charpentier T Wang X Qi S Han B Wu T Terra R Lamarre A Wu J 《The Journal of biological chemistry》2011,286(48):41135-41152
Erythropoietin-producing hepatocellular kinases (Eph kinases) constitute the largest family of cell membrane receptor tyrosine kinases, and their ligand ephrins are also cell surface molecules. Because of promiscuous interaction between Ephs and ephrins, there is considerable redundancy in this system, reflecting the essential roles of these molecules in the biological system through evolution. In this study, both Efnb1 and Efnb2 were null-mutated in the T cell compartment of mice through loxP-mediated gene deletion. Mice with this double conditional mutation (double KO mice) showed reduced thymus and spleen size and cellularity. There was a significant decrease in the DN4, double positive, and single positive thymocyte subpopulations and mature CD4 and CD8 cells in the periphery. dKO thymocytes and peripheral T cells failed to compete with their WT counterparts in irradiated recipients, and the T cells showed compromised ability of homeostatic expansion. dKO naive T cells were inferior in differentiating into Th1 and Th17 effectors in vitro. The dKO mice showed diminished immune response against LCMV infection. Mechanistic studies revealed that IL-6 signaling in dKO T cells was compromised, in terms of abated induction of STAT3 phosphorylation upon IL-6 stimulation. This defect likely contributed to the observed in vitro and in vivo phenotype in dKO mice. This study revealed novel roles of Efnb1 and Efnb2 in T cell development and function. 相似文献
999.
Monjane AL Harkins GW Martin DP Lemey P Lefeuvre P Shepherd DN Oluwafemi S Simuyandi M Zinga I Komba EK Lakoutene DP Mandakombo N Mboukoulida J Semballa S Tagne A Tiendrébéogo F Erdmann JB van Antwerpen T Owor BE Flett B Ramusi M Windram OP Syed R Lett JM Briddon RW Markham PG Rybicki EP Varsani A 《Journal of virology》2011,85(18):9623-9636
Maize streak virus strain A (MSV-A), the causal agent of maize streak disease, is today one of the most serious biotic threats to African food security. Determining where MSV-A originated and how it spread transcontinentally could yield valuable insights into its historical emergence as a crop pathogen. Similarly, determining where the major extant MSV-A lineages arose could identify geographical hot spots of MSV evolution. Here, we use model-based phylogeographic analyses of 353 fully sequenced MSV-A isolates to reconstruct a plausible history of MSV-A movements over the past 150 years. We show that since the probable emergence of MSV-A in southern Africa around 1863, the virus spread transcontinentally at an average rate of 32.5 km/year (95% highest probability density interval, 15.6 to 51.6 km/year). Using distinctive patterns of nucleotide variation caused by 20 unique intra-MSV-A recombination events, we tentatively classified the MSV-A isolates into 24 easily discernible lineages. Despite many of these lineages displaying distinct geographical distributions, it is apparent that almost all have emerged within the past 4 decades from either southern or east-central Africa. Collectively, our results suggest that regular analysis of MSV-A genomes within these diversification hot spots could be used to monitor the emergence of future MSV-A lineages that could affect maize cultivation in Africa. 相似文献
1000.
Coutinho TA Imada Y de Barcellos DE de Oliveira SJ Moreno AM 《Journal of microbiological methods》2011,84(1):27-32
One hundred and fifty-one Erysipelothrix spp. isolates from diseased and carrier swine from Brazil were identified by PCR, submitted to serotyping and analyzed by amplified fragment length polymorphism with a single enzyme (AFLP).Reference strains from Australia and the United Kingdom were also examined. The 151 strains were classified into 18 different serotypes (1a, 1b, 2a, 2b, 4, 5, 6, 7, 8, 10, 11, 12, 15, 17, 19, 21, 24 and 25), being serotype 2b the most frequent (39.7%). By associating serotyping and PCR results, it was possible to identify 146 strains as E. rhusiopathiae and five strains as E. tonsillarum. Despite the fact that for this genus AFLP did not cluster all isolates according to serotype, origin, disease or isolation data, the execution of the technique was easy and fast, demonstrating high discriminatory power. The results produced by the AFLP analysis of Erysipelothrix spp. could also support its use as a discriminatory tool for E. rhusiopathiae and E. tonsillarum species. 相似文献