全文获取类型
收费全文 | 2366篇 |
免费 | 335篇 |
出版年
2022年 | 15篇 |
2021年 | 30篇 |
2020年 | 23篇 |
2019年 | 23篇 |
2018年 | 34篇 |
2017年 | 23篇 |
2016年 | 57篇 |
2015年 | 90篇 |
2014年 | 121篇 |
2013年 | 117篇 |
2012年 | 114篇 |
2011年 | 116篇 |
2010年 | 93篇 |
2009年 | 82篇 |
2008年 | 110篇 |
2007年 | 115篇 |
2006年 | 72篇 |
2005年 | 92篇 |
2004年 | 95篇 |
2003年 | 97篇 |
2002年 | 98篇 |
2001年 | 88篇 |
2000年 | 84篇 |
1999年 | 65篇 |
1998年 | 33篇 |
1997年 | 31篇 |
1996年 | 36篇 |
1995年 | 34篇 |
1994年 | 37篇 |
1993年 | 30篇 |
1992年 | 66篇 |
1991年 | 58篇 |
1990年 | 45篇 |
1989年 | 54篇 |
1988年 | 39篇 |
1987年 | 26篇 |
1986年 | 33篇 |
1985年 | 32篇 |
1984年 | 23篇 |
1983年 | 18篇 |
1982年 | 19篇 |
1981年 | 20篇 |
1980年 | 16篇 |
1979年 | 14篇 |
1978年 | 18篇 |
1975年 | 18篇 |
1974年 | 17篇 |
1973年 | 14篇 |
1972年 | 11篇 |
1968年 | 13篇 |
排序方式: 共有2701条查询结果,搜索用时 15 毫秒
151.
Even Moland Stephanie M. Carlson David Villegas‐Ríos Jrgen Ree Wiig Esben Moland Olsen 《Ecology and evolution》2019,9(11):6480-6491
Harvesting can have profound impacts on the ecology and evolution of marine populations. However, little is known about the strength and direction of fisheries‐induced selection acting on multiple traits in the wild. Here, we used acoustic telemetry to directly monitor individual behavior and fate in an intensively harvested species, the European lobster (Homarus gammarus, n = 100), in southern Norway. Overall, 24% of the tracked lobsters survived the two‐month harvest season within the study area. Our results indicated that local survival was not random with respect to phenotype. We found no clear support for fisheries‐induced selection acting directly on body size. However, lobsters with large crusher claws relative to their body size, typical of socially dominant individuals, appeared at higher risk of being captured in the conventional trap fishery. We also detected a fine‐scale spatial gradient in survival. After accounting for this gradient, individuals displaying larger home ranges were more likely to survive the harvest season. Finally, we found significant repeatabilities for lobster behavior on a monthly timescale, indicating that individual behavioral attributes tended to persist and may reflect personality. Our study therefore provides empirical support for the need to consider an evolutionary enlightened approach to fisheries management that considers the influence of harvest on multiple traits of target species. 相似文献
152.
Coagulation factor VIIa (FVIIa) belongs to a family of proteases being part of the stepwise, self-amplifying blood coagulation cascade. To investigate the impact of the mutation Met(298{156})Lys in FVIIa, we replaced the Gly(283{140})-Met(298{156}) loop with the corresponding loop of factor Xa. The resulting variant exhibited increased intrinsic activity, concurrent with maturation of the active site, a less accessible N-terminus, and, interestingly, an altered macromolecular substrate specificity reflected in an increased ability to cleave factor IX (FIX) and a decreased rate of FX activation compared to that of wild-type FVIIa. In complex with tissue factor, activation of FIX, but not of FX, returned to normal. Deconvolution of the loop graft in order to identify important side chain substitutions resulted in the mutant Val(158{21})Asp/Leu(287{144})Thr/Ala(294{152})Ser/Glu(296{154}) Ile/Met(298{156})Lys-FVIIa with almost the same activity and specificity profile. We conclude that a lysine residue in position 298{156} of FVIIa requires a hydrophilic environment to be fully accommodated. This position appears critical for substrate specificity among the proteases of the blood coagulation cascade due to its prominent position in the macromolecular exosite and possibly via its interaction with the corresponding position in the substrate (i.e. FIX or FX). 相似文献
153.
Objective: Our aim was to examine whether secular trends in childhood overweight and obesity during five decades could be explained by economic growth. Research Methods and Procedures: Annual measurements of height and weight were available for all children born between 1930 and 1983 attending primary school in the Copenhagen Municipality: 165,389 boys and 163,609 girls from the age of 7 through 13 years. After computerization, we calculated BMI (kg/m2) and estimated the prevalence of overweight and obesity, according to international age‐ and gender‐specific criteria, by year of birth and of measurement, and separately by each age group and gender. Economic growth was indicated by the Gross National Product and the overall consumption per capita, adjusted for inflation. Results: The prevalence of overweight occurred in phases: an increase from 1930 until the 1950s, followed by a plateau period between the 1950s and the 1960s and a steep increase thereafter. This pattern was apparent across all age groups and in both genders. Obesity trends showed a similar phase pattern; the prevalence remained relatively stable from 1930 until the 1940s, increased until the mid‐1950s, followed by a plateau until 1965, and thereafter a second steep increase. Obesity trends were similar among boys across all age groups, although only among girls from 11 to 13 years of age. In both genders, increments were most pronounced in the upper BMI percentiles. After stagnation until 1947, the economic growth indicators showed a steady increase; i.e., after the first increase started in overweight and obesity, whether analyzed by year of birth or year of measurement, there were no indications of phases in the rise thereafter. Discussion: Prevalence of overweight and obesity among Danish children rose in phases, which were not paralleled by trends in economic growth. The macroeconomic growth indicators seem inappropriate as proxies for the environmental exposures that have elicited the obesity epidemic. 相似文献
154.
Spatial, temporal, and species variation in prevalence of influenza A viruses in wild migratory birds 总被引:2,自引:0,他引:2
Munster VJ Baas C Lexmond P Waldenström J Wallensten A Fransson T Rimmelzwaan GF Beyer WE Schutten M Olsen B Osterhaus AD Fouchier RA 《PLoS pathogens》2007,3(5):e61
Although extensive data exist on avian influenza in wild birds in North America, limited information is available from elsewhere, including Europe. Here, molecular diagnostic tools were employed for high-throughput surveillance of migratory birds, as an alternative to classical labor-intensive methods of virus isolation in eggs. This study included 36,809 samples from 323 bird species belonging to 18 orders, of which only 25 species of three orders were positive for influenza A virus. Information on species, locations, and timing is provided for all samples tested. Seven previously unknown host species for avian influenza virus were identified: barnacle goose, bean goose, brent goose, pink-footed goose, bewick's swan, common gull, and guillemot. Dabbling ducks were more frequently infected than other ducks and Anseriformes; this distinction was probably related to bird behavior rather than population sizes. Waders did not appear to play a role in the epidemiology of avian influenza in Europe, in contrast to the Americas. The high virus prevalence in ducks in Europe in spring as compared with North America could explain the differences in virus-host ecology between these continents. Most influenza A virus subtypes were detected in ducks, but H13 and H16 subtypes were detected primarily in gulls. Viruses of subtype H6 were more promiscuous in host range than other subtypes. Temporal and spatial variation in influenza virus prevalence in wild birds was observed, with influenza A virus prevalence varying by sampling location; this is probably related to migration patterns from northeast to southwest and a higher prevalence farther north along the flyways. We discuss the ecology and epidemiology of avian influenza A virus in wild birds in relation to host ecology and compare our results with published studies. These data are useful for designing new surveillance programs and are particularly relevant due to increased interest in avian influenza in wild birds. 相似文献
155.
Synaptic vesicles dock to the plasma membrane at synapses to facilitate rapid exocytosis. Docking was originally proposed to require the soluble N-ethylmaleimide–sensitive fusion attachment protein receptor (SNARE) proteins; however, perturbation studies suggested that docking was independent of the SNARE proteins. We now find that the SNARE protein syntaxin is required for docking of all vesicles at synapses in the nematode Caenorhabditis elegans . The active zone protein UNC-13, which interacts with syntaxin, is also required for docking in the active zone. The docking defects in unc-13 mutants can be fully rescued by overexpressing a constitutively open form of syntaxin, but not by wild-type syntaxin. These experiments support a model for docking in which UNC-13 converts syntaxin from the closed to the open state, and open syntaxin acts directly in docking vesicles to the plasma membrane. These data provide a molecular basis for synaptic vesicle docking. 相似文献
156.
157.
Robert D. Hoffmann Lene I. Olsen Chukwuebuka V. Ezike Jesper T. Pedersen Raffaele Manstretta Rosa L. Lpez-Marqus Michael Palmgren 《Physiologia plantarum》2019,166(3):848-861
Plasma membrane H+‐ATPase pumps build up the electrochemical H+ gradients that energize most other transport processes into and out of plant cells through channel proteins and secondary active carriers. In Arabidopsis thaliana, the AUTOINHIBITED PLASMA MEMBRANE H+‐ATPases AHA1, AHA2 and AHA7 are predominant in root epidermal cells. In contrast to other H+‐ATPases, we find that AHA7 is autoinhibited by a sequence present in the extracellular loop between transmembrane segments 7 and 8. Autoinhibition of pump activity was regulated by extracellular pH, suggesting negative feedback regulation of AHA7 during establishment of an H+ gradient. Due to genetic redundancy, it has proven difficult to test the role of AHA2 and AHA7, and mutant phenotypes have previously only been observed under nutrient stress conditions. Here, we investigated root and root hair growth under normal conditions in single and double mutants of AHA2 and AHA7. We find that AHA2 drives root cell expansion during growth but that, unexpectedly, restriction of root hair elongation is dependent on AHA2 and AHA7, with each having different roles in this process. 相似文献
158.
159.
B. J. Gurley M. Marx K. Olsen 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1995,670(2):358-364
Recent developments in restricted-access media (RAM) liquid chromatography make the simultaneous determination of total and free phenytoin concentrations possible by direct injection of drug-containing serum samples. A comparison of phenytoin free fraction determination by ultrafiltration coupled with fluorescence polarization immunoassay (TDX) to an improved direct injection RAM-HPLC method is presented. Our improved method differs from those previously reported with regard to column type, mobile-phase composition, and column temperature. Replicate samples analyzed by each method yielded similar values for serum phenytoin free fraction. 相似文献
160.
Michael R. Heaven Anthony W. Herren Daniel L. Flint Natasha L. Pacheco Jiangtao Li Alice Tang Fatima Khan James E. Goldman Brett S. Phinney Michelle L. Olsen 《Molecular & cellular proteomics : MCP》2022,21(1):100180
Alexander disease (AxD) is a rare and fatal neurodegenerative disorder caused by mutations in the gene encoding glial fibrillary acidic protein (GFAP). In this report, a mouse model of AxD (GFAPTg;Gfap+/R236H) was analyzed that contains a heterozygous R236H point mutation in murine Gfap as well as a transgene with a GFAP promoter to overexpress human GFAP. Using label-free quantitative proteomic comparisons of brain tissue from GFAPTg;Gfap+/R236H versus wild-type mice confirmed upregulation of the glutathione metabolism pathway and indicated proteins were elevated in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which had not been reported previously in AxD. Relative protein-level differences were confirmed by a targeted proteomics assay, including proteins related to astrocytes and oligodendrocytes. Of particular interest was the decreased level of the oligodendrocyte protein, 2-hydroxyacylsphingosine 1-beta-galactosyltransferase (Ugt8), since Ugt8-deficient mice exhibit a phenotype similar to GFAPTg;Gfap+/R236H mice (e.g., tremors, ataxia, hind-limb paralysis). In addition, decreased levels of myelin-associated proteins were found in the GFAPTg;Gfap+/R236H mice, consistent with the role of Ugt8 in myelin synthesis. Fabp7 upregulation in GFAPTg;Gfap+/R236H mice was also selected for further investigation due to its uncharacterized association to AxD, critical function in astrocyte proliferation, and functional ability to inhibit the anti-inflammatory PPAR signaling pathway in models of amyotrophic lateral sclerosis (ALS). Within Gfap+ astrocytes, Fabp7 was markedly increased in the hippocampus, a brain region subjected to extensive pathology and chronic reactive gliosis in GFAPTg;Gfap+/R236H mice. Last, to determine whether the findings in GFAPTg;Gfap+/R236H mice are present in the human condition, AxD patient and control samples were analyzed by Western blot, which indicated that Type I AxD patients have a significant fourfold upregulation of FABP7. However, immunohistochemistry analysis showed that UGT8 accumulates in AxD patient subpial brain regions where abundant amounts of Rosenthal fibers are located, which was not observed in the GFAPTg;Gfap+/R236H mice. 相似文献