首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   3769篇
  免费   337篇
  4106篇
  2021年   40篇
  2020年   31篇
  2019年   34篇
  2018年   36篇
  2017年   40篇
  2016年   59篇
  2015年   108篇
  2014年   139篇
  2013年   134篇
  2012年   145篇
  2011年   187篇
  2010年   90篇
  2009年   114篇
  2008年   142篇
  2007年   131篇
  2006年   139篇
  2005年   132篇
  2004年   111篇
  2003年   115篇
  2002年   93篇
  2001年   101篇
  2000年   117篇
  1999年   97篇
  1998年   45篇
  1997年   54篇
  1996年   53篇
  1994年   30篇
  1993年   39篇
  1992年   78篇
  1991年   89篇
  1990年   79篇
  1989年   69篇
  1988年   70篇
  1987年   52篇
  1986年   55篇
  1985年   78篇
  1984年   82篇
  1983年   69篇
  1982年   55篇
  1981年   45篇
  1980年   46篇
  1979年   61篇
  1978年   53篇
  1977年   44篇
  1976年   36篇
  1975年   39篇
  1974年   45篇
  1973年   26篇
  1972年   36篇
  1969年   26篇
排序方式: 共有4106条查询结果,搜索用时 0 毫秒
81.
The results of a pilot-scale phytoremediation study are reported in this paper. Small plots of trees established on a closed municipal waste landfill site were irrigated with recovered groundwater containing 1,4-dioxane (dioxane) and other volatile organic compounds (VOCs). The plots were managed to minimize the leaching of irrigation water, and leaching was quantified by the use of bromide tracer. Results indicated that the dioxane (2.5 μg/L) was effectively removed, probably via phytovolatilization, and that a full-scale phytoremediation system could be used. A system is now in place at the site in which the recovered groundwater can be treated using two different approaches. A physical treatment system (PTS) will be used during the winter months, and a 12 ha phytoremediation system (stands of coniferous trees) will be used during the growing season. The PTS removes VOCs using an air-stripper, and destroys dioxane using a photo-catalytic oxidation process. Treated water will be routed to the local sewer system. The phytoremediation system, located on the landfill, will be irrigated with effluent from the PTS air-stripper containing dioxane. Seasonal use of the phytoremediation system will reduce reliance on the photo-catalytic oxidation process that is extremely energy consumptive and expensive to operate.  相似文献   
82.
83.
Niemann-Pick Type C (NPC) disease is an autosomal recessive neurodegenerative disorder caused in most cases by mutations in the NPC1 gene. NPC1-deficiency is characterized by late endosomal accumulation of cholesterol, impaired cholesterol homeostasis, and a broad range of other cellular abnormalities. Although neuronal abnormalities and glial activation are observed in nearly all areas of the brain, the most severe consequence of NPC1-deficiency is a near complete loss of Purkinje neurons in the cerebellum. The link between cholesterol trafficking and NPC pathogenesis is not yet clear; however, increased oxidative stress in symptomatic NPC disease, increases in mitochondrial cholesterol, and alterations in autophagy/mitophagy suggest that mitochondria play a role in NPC disease pathology. Alterations in mitochondrial function affect energy and neurotransmitter metabolism, and are particularly harmful to the central nervous system. To investigate early metabolic alterations that could affect NPC disease progression, we performed metabolomics analyses of different brain regions from age-matched wildtype and Npc1 -/- mice at pre-symptomatic, early symptomatic and late stage disease by 1H-NMR spectroscopy. Metabolic profiling revealed markedly increased lactate and decreased acetate/acetyl-CoA levels in Npc1 -/- cerebellum and cerebral cortex at all ages. Protein and gene expression analyses indicated a pre-symptomatic deficiency in the oxidative decarboxylation of pyruvate to acetyl-CoA, and an upregulation of glycolytic gene expression at the early symptomatic stage. We also observed a pre-symptomatic increase in several indicators of oxidative stress and antioxidant response systems in Npc1 -/- cerebellum. Our findings suggest that energy metabolism and oxidative stress may present additional therapeutic targets in NPC disease, especially if intervention can be started at an early stage of the disease.  相似文献   
84.
Coral Reefs - While tropical sea cucumbers are among the most conspicuous mobile invertebrates on coral reefs, information on their population biology and ecology is limited, particularly...  相似文献   
85.
Regulation of arrestin binding by rhodopsin phosphorylation level   总被引:1,自引:0,他引:1  
Arrestins ensure the timely termination of receptor signaling. The role of rhodopsin phosphorylation in visual arrestin binding was established more than 20 years ago, but the effects of the number of receptor-attached phosphates on this interaction remain controversial. Here we use purified rhodopsin fractions with carefully quantified content of individual phosphorylated rhodopsin species to elucidate the impact of phosphorylation level on arrestin interaction with three biologically relevant functional forms of rhodopsin: light-activated and dark phosphorhodopsin and phospho-opsin. We found that a single receptor-attached phosphate does not facilitate arrestin binding, two are necessary to induce high affinity interaction, and three phosphates fully activate arrestin. Higher phosphorylation levels do not increase the stability of arrestin complex with light-activated rhodopsin but enhance its binding to the dark phosphorhodopsin and phospho-opsin. The complex of arrestin with hyperphosphorylated light-activated rhodopsin is less sensitive to high salt and appears to release retinal faster. These data suggest that arrestin likely quenches rhodopsin signaling after the third phosphate is added by rhodopsin kinase. The complex of arrestin with heavily phosphorylated rhodopsin, which appears to form in certain disease states, has distinct characteristics that may contribute to the phenotype of these visual disorders.  相似文献   
86.
In the last decade, research into the molecular determinants of aging has progressed rapidly and much of this progress can be attributed to studies in invertebrate eukaryotic model organisms. Of these, single-celled yeast is the least complicated and most amenable to genetic and molecular manipulations. Supporting the use of this organism for aging research, increasing evidence has accumulated that a subset of pathways influencing longevity in yeast are conserved in other eukaryotes, including mammals. Here we briefly outline aging in yeast and describe recent findings that continue to keep this “simple” eukaryote at the forefront of aging research.  相似文献   
87.
In this article, Jean-Fran?ois Guégan and Clive Kennedy propose an alternative explanation for the confounding effects of host geographical range and sampling effort on parasite species richness using pathway analysis procedure. They suggest that much of the species richness revealed by sampling effort is also a reflection of host range. Thus, the total contribution of host range logically incorporates a contribution from sampling effort. The implications of indirect effects of host range on richness estimates have not previously been discussed, and the authors here attempt to redress the balance. The contribution of host range to richness, as derived from control of sampling effort on richness estimates, therefore, is a mathematical expression that does not take into account the cause-and-effect nature of things.  相似文献   
88.
Konev AY  Yan CM  Acevedo D  Kennedy C  Ward E  Lim A  Tickoo S  Karpen GH 《Genetics》2003,165(4):2039-2053
Heterochromatin is a major component of higher eukaryotic genomes, but progress in understanding the molecular structure and composition of heterochromatin has lagged behind the production of relatively complete euchromatic genome sequences. The introduction of single-copy molecular-genetic entry points can greatly facilitate structure and sequence analysis of heterochromatic regions that are rich in repeated DNA. In this study, we report the isolation of 502 new P-element insertions into Drosophila melanogaster centric heterochromatin, generated in nine different genetic screens that relied on mosaic silencing (position-effect variegation, or PEV) of the yellow gene present in the transposon. The highest frequencies of recovery of variegating insertions were observed when centric insertions were used as the source for mobilization. We propose that the increased recovery of variegating insertions from heterochromatic starting sites may result from the physical proximity of different heterochromatic regions in germline nuclei or from the association of mobilizing elements with heterochromatin proteins. High frequencies of variegating insertions were also recovered when a potent suppressor of PEV (an extra Y chromosome) was present in both the mobilization and selection generations, presumably due to the effects of chromatin structure on P-element mobilization, insertion, and phenotypic selection. Finally, fewer variegating insertions were recovered after mobilization in females, in comparison to males, which may reflect differences in heterochromatin structure in the female and male germlines. FISH localization of a subset of the insertions confirmed that 98% of the variegating lines contain heterochromatic insertions and that these schemes produce a broader distribution of insertion sites. The results of these schemes have identified the most efficient methods for generating centric heterochromatin P insertions. In addition, the large collection of insertions produced by these screens provides molecular-genetic entry points for mapping, sequencing, and functional analysis of Drosophila heterochromatin.  相似文献   
89.
The molybdenum- and iron-containing protein components of nitrogenase purified from Klebsiella pneumoniae, Azotobacter vinelandii, Azotobacter chroococcum and Rhizobium japonicum bacteroids all gave either one or two protein-staining bands after sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, depending on the commercial brand of sodium dodecyl sulphate used. The single band obtained with K. pneumoniae Mo-Fe protein when some commercial brands of sodium dodecyl sulphate were used in the preparation of the electrode buffer was resolved into two bands by the addition of 0.01% (v/v) dodecanol to the buffer. Protein extracted from the two bands obtained after electrophoresis of K. pneumoniae Mo-Fe protein gave unique and distinct peptide 'maps' after tryptic digestion. Undissociated Mo-Fe protein contained both sets of tryptic peptides. These data are consistent with Mo-Fe protein from K. pneumoniae being composed of non-identical subunits. Amino acid analyses of the subunit proteins revealed some clear differences in amino acid content, but the two subunits showed close compositional relatedness, with a different index [Metzer, H., Shapiro, M.B., Mosiman, J.E. & Vinton, J.G. (1968) Nature (London) 219, 1166-1168] of 4.7.  相似文献   
90.
Diglyceride kinase (diacylglycerol kinase, E.C. 2.7.1.-), an enzyme localized in the inner membrane of Escherichia coli, has been purified about 600-fold. The purified enzyme exhibits an absolute requirement for magnesium ion; its activity toward both lipid and nucleotide substrates is stimulated by diphosphatidylglycerol or other phospholipids. Adenine nucleotides are much better substrates for the enzyme than are other purine or pyrimidine nucleotides. The purified enzyme preparation catalyzes the phosphorylation of a number of lipids, including ceramide and several ceramide and diacylglycerol-like analogs. The broad lipid substrate specificity of diglyceride kinase suggests that this enzyme may function in vivo for the phosphorylation of an acceptor other than diacylglycerol.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号