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   1552篇
  免费   131篇
  2023年   4篇
  2022年   3篇
  2021年   25篇
  2020年   18篇
  2019年   20篇
  2018年   25篇
  2017年   25篇
  2016年   35篇
  2015年   77篇
  2014年   93篇
  2013年   107篇
  2012年   124篇
  2011年   109篇
  2010年   89篇
  2009年   75篇
  2008年   117篇
  2007年   100篇
  2006年   94篇
  2005年   93篇
  2004年   86篇
  2003年   78篇
  2002年   95篇
  2001年   16篇
  2000年   10篇
  1999年   25篇
  1998年   17篇
  1997年   14篇
  1996年   17篇
  1995年   11篇
  1994年   15篇
  1993年   11篇
  1992年   9篇
  1991年   10篇
  1990年   7篇
  1989年   2篇
  1987年   6篇
  1986年   1篇
  1985年   4篇
  1984年   1篇
  1983年   1篇
  1982年   1篇
  1981年   2篇
  1980年   2篇
  1979年   1篇
  1977年   1篇
  1976年   1篇
  1973年   2篇
  1972年   1篇
  1957年   1篇
  1921年   1篇
排序方式: 共有1683条查询结果,搜索用时 125 毫秒
111.
Huntington’s disease (HD) is an inherited progressive neurodegenerative disorder caused by an expanded CAG repeat in exon 1 of the huntingtin gene (HTT). The primary neuropathology of HD has been attributed to the preferential degeneration of medium spiny neurons (MSN) in the striatum. Reports on striatal neurogenesis have been a subject of debate; nevertheless, it should be considered as an endogenous attempt to repair the brain. The subventricular zone (SVZ) might offer a close-by region to supply the degenerated striatum with new cells. Previously, we have demonstrated that R6/2 mice, a widely used preclinical model representing an early onset HD, showed reduced olfactory bulb (OB) neurogenesis but induced striatal migration of neuroblasts without affecting the proliferation of neural progenitor cell (NPCs) in the SVZ. The present study revisits these findings, using a clinically more relevant transgenic rat model of late onset HD (tgHD rats) carrying the human HTT gene with 51 CAG repeats and mimicking many of the neuropathological features of HD seen in patients. We demonstrate that cell proliferation is reduced in the SVZ and OB of tgHD rats compared to WT rats. In the OB of tgHD rats, although cell survival was reduced, the frequency of neuronal differentiation was not altered in the granule cell layer (GCL) compared to the WT rats. However, an increased frequency of dopamenergic neuronal differentiation was noticed in the glomerular layer (GLOM) of tgHD rats. Besides this, we observed a selective proliferation of neuroblasts in the adjacent striatum of tgHD rats. There was no evidence for neuronal maturation and survival of these striatal neuroblasts. Therefore, the functional role of these invading neuroblasts still needs to be determined, but they might offer an endogenous alternative for stem or neuronal cell transplantation strategies.  相似文献   
112.
Illegal harvest is recognized as a widespread problem in natural resource management. The use of multiple methods for quantifying illegal harvest has been widely recommended yet infrequently applied. We used a mixed-method approach to evaluate the extent, character, and motivations of illegal gillnet fishing in Lake Hovsgol National Park, Mongolia and its impact on the lake’s fish populations, especially that of the endangered endemic Hovsgol grayling (Thymallus nigrescens). Surveys for derelict fishing gear indicate that gillnet fishing is widespread and increasing and that fishers generally use 3–4 cm mesh gillnet. Interviews with resident herders and park rangers suggest that many residents fish for subsistence during the spring grayling spawning migration and that some residents fish commercially year-round. Interviewed herders and rangers generally agree that fish population sizes are decreasing but are divided on the causes and solutions. Biological monitoring indicates that the gillnet mesh sizes used by fishers efficiently target Hovsgol grayling. Of the five species sampled in the monitoring program, only burbot (Lota lota) showed a significant decrease in population abundance from 2009–2013. However, grayling, burbot, and roach (Rutilus rutilus) all showed significant declines in average body size, suggesting a negative fishing impact. Data-poor stock assessment methods suggest that the fishing effort equivalent to each resident family fishing 50-m of gillnet 11–15 nights per year would be sufficient to overexploit the grayling population. Results from the derelict fishing gear survey and interviews suggest that this level of effort is not implausible. Overall, we demonstrate the ability for a mixed-method approach to effectively describe an illegal fishery and suggest that these methods be used to assess illegal fishing and its impacts in other protected areas.  相似文献   
113.
Metabolic disorders, like diabetes and obesity, are pathogenic outcomes of imbalance in glucose metabolism. Nutrient excess and mitochondrial imbalance are implicated in dysfunctional glucose metabolism with age. We used conplastic mouse strains with defined mitochondrial DNA (mtDNA) mutations on a common nuclear genomic background, and administered a high-fat diet up to 18 months of age. The conplastic mouse strain B6-mtFVB, with a mutation in the mt-Atp8 gene, conferred β-cell dysfunction and impaired glucose tolerance after high-fat diet. To our surprise, despite of this functional deficit, blood glucose levels adapted to perturbations with age. Blood glucose levels were particularly sensitive to perturbations at the early age of 3 to 6 months. Overall the dynamics consisted of a peak between 3–6 months followed by adaptation by 12 months of age. With the help of mathematical modeling we delineate how body weight, insulin and leptin regulate this non-linear blood glucose dynamics. The model predicted a second rise in glucose between 15 and 21 months, which could be experimentally confirmed as a secondary peak. We therefore hypothesize that these two peaks correspond to two sensitive periods of life, where perturbations to the basal metabolism can mark the system for vulnerability to pathologies at later age. Further mathematical modeling may perspectively allow the design of targeted periods for therapeutic interventions and could predict effects on weight loss and insulin levels under conditions of pre-diabetic obesity.  相似文献   
114.
Fishes are one of the most commonly introduced aquatic taxa worldwide, and invasive fish species pose threats to biodiversity and ecosystem function in recipient waters. Considerable research efforts have focused on predicting the invasibility of different fish taxa; however, accurate records detailing the establishment and spread of invasive fishes are lacking for large numbers of fish around the globe. In response to these data limitations, a low-cost method of cataloging and quantifying the temporal and spatial status of fish invasions was explored. Specifically, angler catch data derived from competitive bass angling tournaments was used to document the distribution of 66 non-native populations of black bass (Micropterus spp.) in southern Africa. Additionally, catch data from standardized tournament events were used to assess the abundance and growth of non-native bass populations in southern Africa relative to their native distribution (southern and eastern United States). Differences in metrics of catch per unit effort (average number of fish retained per angler per day), daily bag weights (the average weight of fish retained per angler), and average fish weight were assessed using catch data from 14,890 angler days of tournament fishing (11,045 days from South Africa and Zimbabwe; 3,845 days from the United States). No significant differences were found between catch rates, average daily bag weight, or the average fish weight between countries, suggesting that bass populations in southern Africa reach comparable sizes and numbers relative to waters in their native distribution. Given the minimal cost associated with data collection (i.e. records are collected by tournament organizers), the standardized nature of the events, and consistent bias (i.e. selection for the biggest fish in a population), the use of angler catch data represents a novel approach to infer the status and distribution of invasive sport fish.  相似文献   
115.

Background

To achieve more realistic simulations, meteorologists develop and use models with increasing spatial and temporal resolution. The analyzing, comparing, and visualizing of resulting simulations becomes more and more challenging due to the growing amounts and multifaceted character of the data. Various data sources, numerous variables and multiple simulations lead to a complex database. Although a variety of software exists suited for the visualization of meteorological data, none of them fulfills all of the typical domain-specific requirements: support for quasi-standard data formats and different grid types, standard visualization techniques for scalar and vector data, visualization of the context (e.g., topography) and other static data, support for multiple presentation devices used in modern sciences (e.g., virtual reality), a user-friendly interface, and suitability for cooperative work.

Methods and Results

Instead of attempting to develop yet another new visualization system to fulfill all possible needs in this application domain, our approach is to provide a flexible workflow that combines different existing state-of-the-art visualization software components in order to hide the complexity of 3D data visualization tools from the end user. To complete the workflow and to enable the domain scientists to interactively visualize their data without advanced skills in 3D visualization systems, we developed a lightweight custom visualization application (MEVA - multifaceted environmental data visualization application) that supports the most relevant visualization and interaction techniques and can be easily deployed. Specifically, our workflow combines a variety of different data abstraction methods provided by a state-of-the-art 3D visualization application with the interaction and presentation features of a computer-games engine. Our customized application includes solutions for the analysis of multirun data, specifically with respect to data uncertainty and differences between simulation runs. In an iterative development process, our easy-to-use application was developed in close cooperation with meteorologists and visualization experts. The usability of the application has been validated with user tests. We report on how this application supports the users to prove and disprove existing hypotheses and discover new insights. In addition, the application has been used at public events to communicate research results.  相似文献   
116.
Lipoteichoic acids (LTA) are polymers of alternating units of a polyhydroxy alkane, including glycerol and ribitol, and phosphoric acid, joined to form phosphodiester units that are found in the envelope of Gram-positive bacteria. Here we review four different types of LTA that can be distinguished on the basis of their chemical structure and describe recent advances in the biosynthesis pathway for type I LTA, d-alanylated polyglycerol-phosphate linked to di-glucosyl-diacylglycerol. The physiological functions of type I LTA are discussed in the context of inhibitors that block their synthesis and of mutants with discrete synthesis defects. Research on LTA structure and function represents a large frontier that has been investigated in only few Gram-positive bacteria.  相似文献   
117.
[Correction Notice: An erratum for this article was reported in Vol 20(3) of Dreaming (see record 2010-17362-006). In the article, a third author was not listed in the byline and some acknowledgment information was also missing: Third Co-Author: Anja S. G?ritz, University of Würzburg, Würzburg, Germany Additional Acknowledgment: We thank the operators of the sites www.panopia.de, www.yougov.de, and www.studivz.net for providing participants. This work was in part supported by DFG grant GO 1107/4-1 to G?ritz. The online version of the article has been corrected.] Recently, a large meta-analysis showed that women tend to recall their dreams more often than men. Despite this robust finding, studies focused on explaining the gender difference in dream recall frequency are scarce. The present findings of an online survey indicate that sex role orientation—expressivity/femininity—was related to dream recall frequency but did not fully explain the gender difference in dream recall frequency. Future studies should investigate other variables—in addition to sex role orientation—like verbal memory, recall of emotional experiences, and/or frequency of talking about emotional matters that might play a role in explaining the gender difference in dream recall. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
118.
Reports an error in "Gender, sex role orientation, and dream recall frequency" by Michael Schredl and Olaf Lahl (Dreaming, 2010[Mar], Vol 20[1], 19-24). In the article, a third author was not listed in the byline and some acknowledgment information was also missing: Third Co-Author: Anja S. G?ritz, University of Würzburg, Würzburg, Germany. The name appears in this record. Additional Acknowledgment: We thank the operators of the sites www.panopia.de, www.yougov.de, and www.studivz.net for providing participants. This work was in part supported by DFG grant GO 1107/4-1 to G?ritz. The online version of the article has been corrected. (The following abstract of the original article appeared in record 2010-05656-002.) Recently, a large meta-analysis showed that women tend to recall their dreams more often than men. Despite this robust finding, studies focused on explaining the gender difference in dream recall frequency are scarce. The present findings of an online survey indicate that sex role orientation—expressivity/femininity—was related to dream recall frequency but did not fully explain the gender difference in dream recall frequency. Future studies should investigate other variables—in addition to sex role orientation—like verbal memory, recall of emotional experiences, and/or frequency of talking about emotional matters that might play a role in explaining the gender difference in dream recall. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
119.
The human pathogen Staphylococcus aureus requires cell wall anchored surface proteins to cause disease. During cell division, surface proteins with YSIRK signal peptides are secreted into the cross-wall, a layer of newly synthesized peptidoglycan between separating daughter cells. The molecular determinants for the trafficking of surface proteins are, however, still unknown. We screened mutants with non-redundant transposon insertions by fluorescence-activated cell sorting for reduced deposition of protein A (SpA) into the staphylococcal envelope. Three mutants, each of which harboured transposon insertions in genes for transmembrane proteins, displayed greatly reduced envelope abundance of SpA and surface proteins with YSIRK signal peptides. Characterization of the corresponding mutations identified three transmembrane proteins with abortive infectivity (ABI) domains, elements first described in lactococci for their role in phage exclusion. Mutations in genes for ABI domain proteins, designated spdA, spdB and spdC (surface protein display), diminish the expression of surface proteins with YSIRK signal peptides, but not of precursor proteins with conventional signal peptides. spdA, spdB and spdC mutants display an increase in the thickness of cross-walls and in the relative abundance of staphylococci with cross-walls, suggesting that spd mutations may represent a possible link between staphylococcal cell division and protein secretion.  相似文献   
120.
Crystal structures of polypeptide deformylase (PDF) of Escherichia coli with nickel(II) replacing the native iron(II) have been solved with chloride and formate as metal ligands. The chloro complex is a model for the correct protonation state of the hydrolytic hydroxo ligand and the protonated status of the Glu133 side chain as part of the hydrolytic mechanism. The ambiguity that recently some PDFs have been identified with Zn2+ ion as the active-site centre whereas others are only active with Fe2+ (or Co2+, Ni2+) is discussed with respect to Lewis acid criteria of the metal ion and substrate activation by the CD loop.  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