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   2031篇
  免费   96篇
  国内免费   125篇
  2023年   20篇
  2022年   28篇
  2021年   39篇
  2020年   39篇
  2019年   45篇
  2018年   42篇
  2017年   50篇
  2016年   45篇
  2015年   48篇
  2014年   170篇
  2013年   230篇
  2012年   160篇
  2011年   121篇
  2010年   71篇
  2009年   114篇
  2008年   124篇
  2007年   122篇
  2006年   80篇
  2005年   60篇
  2004年   54篇
  2003年   56篇
  2002年   46篇
  2001年   42篇
  2000年   24篇
  1999年   33篇
  1998年   35篇
  1997年   28篇
  1996年   35篇
  1995年   27篇
  1994年   30篇
  1993年   27篇
  1992年   22篇
  1991年   24篇
  1990年   21篇
  1989年   13篇
  1988年   10篇
  1987年   12篇
  1986年   9篇
  1985年   12篇
  1984年   11篇
  1983年   3篇
  1982年   11篇
  1981年   8篇
  1980年   11篇
  1979年   7篇
  1978年   5篇
  1977年   4篇
  1975年   5篇
  1974年   3篇
  1971年   5篇
排序方式: 共有2252条查询结果,搜索用时 296 毫秒
101.
Members of a family of collagen-binding microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) from Gram-positive bacteria are established virulence factors in several infectious diseases models. Here, we report that these adhesins also can bind C1q and act as inhibitors of the classical complement pathway. Molecular analyses of Cna from Staphylococcus aureus suggested that this prototype MSCRAMM bound to the collagenous domain of C1q and interfered with the interactions of C1r with C1q. As a result, C1r2C1s2 was displaced from C1q, and the C1 complex was deactivated. This novel function of the Cna-like MSCRAMMs represents a potential immune evasion strategy that could be used by numerous Gram-positive pathogens.  相似文献   
102.
The interaction of MinC with FtsZ and its effects on FtsZ polymerization were studied under close to physiological conditions by a combination of biophysical methods. The Min system is a widely conserved mechanism in bacteria that ensures the correct placement of the division machinery at midcell. MinC is the component of this system that effectively interacts with FtsZ and inhibits the formation of the Z-ring. Here we report that MinC produces a concentration-dependent reduction in the size of GTP-induced FtsZ protofilaments (FtsZ-GTP) as demonstrated by analytical ultracentrifugation, dynamic light scattering, fluorescence correlation spectroscopy, and electron microscopy. Our experiments show that, despite being shorter, FtsZ protofilaments maintain their narrow distribution in size in the presence of MinC. The protein had the same effect regardless of its addition prior to or after FtsZ polymerization. Fluorescence anisotropy measurements indicated that MinC bound to FtsZ-GDP with a moderate affinity (apparent KD ∼10 μm at 100 mm KCl and pH 7.5) very close to the MinC concentration corresponding to the midpoint of the inhibition of FtsZ assembly. Only marginal binding of MinC to FtsZ-GTP protofilaments was observed by analytical ultracentrifugation and fluorescence correlation spectroscopy. Remarkably, MinC effects on FtsZ-GTP protofilaments and binding affinity to FtsZ-GDP were strongly dependent on ionic strength, being severely reduced at 500 mm KCl compared with 100 mm KCl. Our results support a mechanism in which MinC interacts with FtsZ-GDP, resulting in smaller protofilaments of defined size and having the same effect on both preassembled and growing FtsZ protofilaments.  相似文献   
103.
Changes in bone remodeling induced by pharmacological and genetic manipulation of β-adrenergic receptor (βAR) signaling in osteoblasts support a role of sympathetic nerves in the regulation of bone remodeling. However, the contribution of endogenous sympathetic outflow and nerve-derived norepinephrine (NE) to bone remodeling under pathophysiological conditions remains unclear. We show here that differentiated osteoblasts, like neurons, express the norepinephrine transporter (NET), exhibit specific NE uptake activity via NET and can catabolize, but not generate, NE. Pharmacological blockade of NE transport by reboxetine induced bone loss in WT mice. Similarly, lack of NE reuptake in norepinephrine transporter (Net)-deficient mice led to reduced bone formation and increased bone resorption, resulting in suboptimal peak bone mass and mechanical properties associated with low sympathetic outflow and high plasma NE levels. Last, daily sympathetic activation induced by mild chronic stress was unable to induce bone loss, unless NET activity was blocked. These findings indicate that the control of endogenous NE release and reuptake by presynaptic neurons and osteoblasts is an important component of the complex homeostatic machinery by which the sympathetic nervous system controls bone remodeling. These findings also suggest that drugs antagonizing NET activity, used for the treatment of hyperactivity disorders, may have deleterious effects on bone accrual.  相似文献   
104.
The Salmonella enterica serovar Typhimurium PhoP/PhoQ system has largely been studied as a paradigmatic two-component regulatory system not only to dissect structural and functional aspects of signal transduction in bacteria but also to gain knowledge about the versatile devices that have evolved allowing a pathogenic bacterium to adjust to or counteract environmental stressful conditions along its life cycle. Mg2+ limitation, acidic pH, and the presence of cationic antimicrobial peptides have been identified as cues that the sensor protein PhoQ can monitor to reprogram Salmonella gene expression to cope with extra- or intracellular challenging conditions. In this work, we show for the first time that long chain unsaturated free fatty acids (LCUFAs) present in Salmonella growth medium are signals specifically detected by PhoQ. We demonstrate that LCUFAs inhibit PhoQ autokinase activity, turning off the expression of the PhoP-dependent regulon. We also show that LCUFAs exert their action independently of their cellular uptake and metabolic utilization by means of the β-oxidative pathway. Our findings put forth the complexity of input signals that can converge to finely tune the activity of the PhoP/PhoQ system. In addition, they provide a new potential biochemical platform for the development of antibacterial strategies to fight against Salmonella infections.  相似文献   
105.
黑龙江省野生东北虎调查管理信息系统的构建   总被引:1,自引:0,他引:1  
文章以黑龙江省野生东北虎(Panthera tigris altaica)野外调查数据为基础,利用地理信息系统技术、计算机技术与野生动物资源调查管理技术,构建了黑龙江省野生东北虎调查管理信息系统。主要运用面向对象程序设计语言C#和ArcGIS Engine嵌入式组件技术以及SQL Server数据库技术,设计并构建东北虎调查管理系统,实现了对野生东北虎调查数据的图形可视化操作管理。同时,结合研究区域内的自然因素和人文因素对调查资源进行动态的空间分析,及时准确地反映出东北虎的种群数量和空间变化规律,并制作出相应的分类专题图及野外分布信息统计图表等。该管理信息系统将有助于野生东北虎种群及栖息地调查数据与资料的科学管理,对于推动我国野生东北虎就地保护和科学管理具有重要意义。  相似文献   
106.
箭叶淫羊藿居群形态及遗传多样性比较研究   总被引:1,自引:0,他引:1  
箭叶淫羊藿(Epimedium sagittatum)是淫羊藿属中分布最广、形态变异最大、分类学最难处理的一个物种,不同箭叶淫羊藿居群其形态、活性成分等差异较大,质量极其不稳定。本实验选择湖北罗田等12个不同的箭叶淫羊藿地理居群,在武汉植物园进行同园栽培,分析其主要形态数量性状及遗传多样性。结果发现箭叶淫羊藿不同居群在形态上表现出各自明显的差异。基于AFLP数据进行的遗传多样性分析显示,各居群聚类关系与地理分布密切相关,柳州居群(LZ)、西南居群(CL、HH、ZY)、华东华中居群(YT、WN、NF、HS、QZ、SG、LY、LT)依次分出。而形态分层聚类分析显示各居群形态变异复杂,只有部分与遗传多样性有一定的相关性。本研究结果对箭叶淫羊藿分类研究及资源筛选具有重要指导作用。  相似文献   
107.
Nuclear medicine physicians are very involved in French's oncology announcement procedure. However, their role needs to be analysed and evaluated. Before diagnosis’ announcement, information provided by nuclear medicine physicians are never neutral for patients. Information must not increase patient's anxiety or false patient's sense of reassurance. In this context, it seems necessary to engage in ethical reflexions about nuclear medicine physicians communication challenges.  相似文献   
108.
为分析西南地区特色猕猴桃(Actinidia Lindl.)的遗传多样性,建立并优化了猕猴桃DNA 多态性分析的AFLP 体系,AFLP 标记体系为300 ng 基因组DNA 用EcoR Ⅰ/Mse Ⅰ (15 U/5 U)于37℃下酶切2 h,加接头后的混合物稀释5 倍用于预扩增,预扩增产物再稀释10 倍后进行选择性扩增.结果表明,筛选的22 对引物进行扩增反应,共得到979 条条带,其中多态性条带为649 条.采用优化的AFLP 体系,对西南地区的10 种猕猴桃50 个样本进行了遗传多样性分析,包括普通品种中华猕猴桃、美味猕猴桃,及特色品种硬毛猕猴桃、毛被猕猴桃、革叶猕猴桃、四萼猕猴桃、狗枣猕猴桃、葛枣猕猴桃、京梨猕猴桃和紫果猕猴,结果表明种内和种间的聚类关系明显;斑果组(sect. Maculatae)和净果组(sect. Leiocarpae)的种间有聚类交叉,并呈现地理区域性分布.  相似文献   
109.
Several populations of long-distance migratory birds are currently suffering steep demographic declines. The identification of the causes of such declines is difficult because population changes may be driven by events occurring in distant geographical areas during different phases of the annual life-cycle of migrants. Furthermore, wintering areas and migration routes of populations of small-sized species are still largely unknown, with few exceptions. In this paper we identified the critical phases of the annual life-cycle that most influence the population dynamics of a small passerine, the Barn Swallow Hirundo rustica. We used information on temporal dynamics of a population breeding in Northern Italy, whose wintering range and timing of migration have been recently described by miniaturised tracking dataloggers. Our results indicated that primary productivity in the wintering grounds in the month when most individuals arrive from autumn migration and primary productivity in an area that is probably a stopover site during spring migration, influenced population dynamics more than habitat conditions at the breeding grounds. By using annual variation in primary productivity at the wintering grounds and stopover sites as predictors, we replicated the observed interannual population changes with great accuracy. However, the steep decline recently suffered by the population could be replicated only by including a constant annual decline in the model, suggesting that changes in primary productivity only predicted the interannual variation around the long-term trend. Our study therefore suggests the existence of critical periods during wintering and migration that may have large impact on population fluctuations of migrant birds.  相似文献   
110.
During the 20th century, population ecology and science in general relied on two very different statistical paradigms to solve its inferential problems: error statistics (also referred to as classical statistics and frequentist statistics) and Bayesian statistics. A great deal of good science was done using these tools, but both schools suffer from technical and philosophical difficulties. At the turning of the 21st century (Royall in Statistical evidence: a likelihood paradigm. Chapman & Hall, London, 1997 ; Lele in The nature of scientific evidence: statistical, philosophical and empirical considerations. The University of Chicago Press, Chicago, pp 191–216, 2004a ), evidential statistics emerged as a seriously contending paradigm. Drawing on and refining elements from error statistics, likelihoodism, Bayesian statistics, information criteria, and robust methods, evidential statistics is a statistical modern synthesis that smoothly incorporates model identification, model uncertainty, model comparison, parameter estimation, parameter uncertainty, pre-data control of error, and post-data strength of evidence into a single coherent framework. We argue that evidential statistics is currently the most effective statistical paradigm to support 21st century science. Despite the power of the evidential paradigm, we think that there is no substitute for learning how to clarify scientific arguments with statistical arguments. In this paper we sketch and relate the conceptual bases of error statistics, Bayesian statistics and evidential statistics. We also discuss a number of misconceptions about the paradigms that have hindered practitioners, as well as some real problems with the error and Bayesian statistical paradigms solved by evidential statistics.  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