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   5809篇
  免费   531篇
  国内免费   1篇
  2023年   28篇
  2022年   74篇
  2021年   148篇
  2020年   71篇
  2019年   108篇
  2018年   117篇
  2017年   108篇
  2016年   166篇
  2015年   300篇
  2014年   296篇
  2013年   392篇
  2012年   553篇
  2011年   485篇
  2010年   337篇
  2009年   291篇
  2008年   366篇
  2007年   409篇
  2006年   387篇
  2005年   323篇
  2004年   306篇
  2003年   299篇
  2002年   225篇
  2001年   45篇
  2000年   41篇
  1999年   43篇
  1998年   60篇
  1997年   22篇
  1996年   35篇
  1995年   26篇
  1994年   21篇
  1993年   29篇
  1992年   18篇
  1991年   13篇
  1990年   17篇
  1989年   24篇
  1988年   17篇
  1987年   9篇
  1986年   8篇
  1985年   6篇
  1984年   13篇
  1983年   6篇
  1982年   11篇
  1981年   6篇
  1980年   9篇
  1979年   6篇
  1977年   9篇
  1976年   5篇
  1975年   7篇
  1974年   14篇
  1973年   7篇
排序方式: 共有6341条查询结果,搜索用时 15 毫秒
991.
Changes in climate conditions, particularly during the Quaternary climatic oscillations, have long been recognized to be important for shaping patterns of species diversity. For species residing in the western Palearctic, two commonly observed genetic patterns resulting from these cycles are as follows: (1) that the numbers and distributions of genetic lineages correspond with the use of geographically distinct glacial refugia and (2) that southern populations are generally more diverse than northern populations (the “southern richness, northern purity” paradigm). To determine whether these patterns hold true for the widespread pest species the winter moth (Operophtera brumata), we genotyped 699 individual winter moths collected from 15 Eurasian countries with 24 polymorphic microsatellite loci. We find strong evidence for the presence of two major genetic clusters that diverged ~18 to ~22 ka, with evidence that secondary contact (i.e., hybridization) resumed ~ 5 ka along a well‐established hybrid zone in Central Europe. This pattern supports the hypothesis that contemporary populations descend from populations that resided in distinct glacial refugia. However, unlike many previous studies of postglacial recolonization, we found no evidence for the “southern richness, northern purity” paradigm. We also find evidence for ongoing gene flow between populations in adjacent Eurasian countries, suggesting that long‐distance dispersal plays an important part in shaping winter moth genetic diversity. In addition, we find that this gene flow is predominantly in a west‐to‐east direction, suggesting that recently debated reports of cyclical outbreaks of winter moth spreading from east to west across Europe are not the result of dispersal.  相似文献   
992.
To complete mitosis, the bridge that links the two daughter cells needs to be cleaved. This step is carried out by the endosomal sorting complex required for transport (ESCRT) machinery. AKTIP, a protein discovered to be associated with telomeres and the nuclear membrane in interphase cells, shares sequence similarities with the ESCRT I component TSG101. Here we present evidence that during mitosis AKTIP is part of the ESCRT machinery at the midbody. AKTIP interacts with the ESCRT I subunit VPS28 and forms a circular supra-structure at the midbody, in close proximity with TSG101 and VPS28 and adjacent to the members of the ESCRT III module CHMP2A, CHMP4B and IST1. Mechanistically, the recruitment of AKTIP is dependent on MKLP1 and independent of CEP55. AKTIP and TSG101 are needed together for the recruitment of the ESCRT III subunit CHMP4B and in parallel for the recruitment of IST1. Alone, the reduction of AKTIP impinges on IST1 and causes multinucleation. Our data altogether reveal that AKTIP is a component of the ESCRT I module and functions in the recruitment of ESCRT III components required for abscission.  相似文献   
993.
994.
As part of a study of the molecular basis of membrane fusion by enveloped viruses, we have used neutron diffraction to study the lamellar (Lα) to inverse hexagonal (HII) phase transition in the phospholipid N-methylated dioleoylphosphatidylethanolamine. This lipid was chosen because its phase transitions are particularly sensitive to the presence of agents that have been demonstrated to promote or inhibit membrane fusion. Two different geometries of neutron diffraction were used: small angle scattering (SANS) and a membrane diffractometer. The SANS measurements were carried out on the SWAN instrument at KEK, Japan, using dispersions of multilamellar vesicles (MLVs). The diffractometer measurements used the V1 instrument at BeNSC-HMI, Germany, with a specially-constructed cell that holds a stack of lipid bilayers in an excess-water state. The two approaches are compared and discussed. Although the diffractometer takes considerably longer to collect the data, it records much higher resolution than the SANS instrument. The samples recorded in the excess-water cell were shown to be well aligned, despite the lipids being fully hydrated, allowing for the production of high-resolution data. Trial measurements performed have demonstrated that sample alignment is preserved throughout the Lα to HII phase transition, thereby opening up possibilities for obtaining high-resolution data from non-lamellar phases.  相似文献   
995.
In this study, we evaluated the efficacy of two different dynamic warm-up conditions, one that was inclusive of open skills (i.e., reactive movements) and one that included only preplanned dynamic activities (i.e., closed skills) on the performance of speed, change of direction speed, vertical jump, and reactive agility in team sport athletes. Fourteen (six male, eight female) junior (mean +/- SD age, 16.3 +/- 0.7 year) basketball players participated in this study. Testing was conducted on 2 separate days using a within-subjects cross-over study design. Each athlete performed a standardized 7-minute warm-up consisting of general dynamic movements and stretching. After the general warm-up, athletes were randomly allocated into one of two groups that performed a dynamic 15-minute warm-up consisting entirely of open or closed skills. Each of the warm-up conditions consisted of five activities of 3 minute duration. At the completion of the warm-up protocol, players completed assessments of reactive agility, speed (5-, 10-, and 20-m sprints), change of direction speed (T-test), and vertical jump. No significant differences (p > 0.05) were detected among warm-up conditions for speed, vertical jump, change of direction speed, and reactive agility performances. The results of this study demonstrate that either open skill or closed skill warm-ups can be used effectively for team sport athletes without compromising performance on open skill and closed skill tasks.  相似文献   
996.
The purposes of this investigation were to evaluate the occurrence of a small amplitude counter-movement (SACM) in SJ (squat jump) trials of elite athletes to determine the efficacy of gross observation and the use of a portable position transducer to determine whether or not a SACM occurred. The subjects (N = 30, 20.1 +/- 3.0 years, 199.0 +/- 8.4 cm, and 87.2 +/- 9.5 kg) were a combination of high-performance (National Team) and elite athletes (Olympian) from the sports of athletics, swimming, and volleyball. All subjects performed SJ trials on a force platform, with a linear position transducer attached to a bar placed across the shoulders. Subjects performed the SJ from a depth that allowed for a 90 degrees knee angle, with the subject's instructed to maintain a 3-second isometric hold preceding the concentric action of the jump. One hundred twenty-five SJ trials were observed for a SACM and analyzed (using the force plate data and position transducer data) for a SACM. Of the 125 SJ trials, 69 trials (55.2%) were observed to have a SACM by the researchers. In the remaining 56 trials, 43 of these trials contained a force unload (>/=10% body mass) before initiation of the concentric action, indicating a SACM. Of the 119 SJ trials where a force unload was observed and detected by the force-time graph, 118 (99.2%) of these trials also showed a change in displacement using the displacement-time graph from the linear position transducer. The results of this study indicate that achieving compliance to protocol in the SJ is difficult, and that gross observation is inadequate in detecting a SACM in the SJ. From a practical perspective, these results suggest that using a force plate or a linear position transducer would allow the strength and conditioning coach to ensure compliance to instructions in the SJ.  相似文献   
997.
Abiotic factors are thought to be primarily responsible for the loss of bacteriophages from the environment, but ingestion of phages by heterotrophs may also play a role in their elimination. Tetrahymena thermophila has been shown to ingest and inactivate bacteriophage T4 in co-incubation experiments. In this study, other Tetrahymena species were co-incubated with T4 with similar results. In addition, T. thermophila was shown to inactivate phages T5 and lambda in co-incubations. Several approaches, including direct visualization by electron microscopy, demonstrated that ingestion is required for T4 inactivation. Mucocysts were shown to have no role in the ingestion of T4. When (35)S-labeled T4 were fed to T. thermophila in a pulse-chase experiment, the degradation of two putative capsid proteins, gp23(*) and hoc, was observed. In addition, a polypeptide with the apparent molecular mass of 52 kDa was synthesized. This suggests that Tetrahymena can use phages as a minor nutrient source in the absence of bacteria.  相似文献   
998.
We challenge the concept of idiopathic parkinsonism (IP) as inevitably progressive neurodegeneration, proposing a natural history of sequential microbial insults with predisposing host response. Proof-of-principle that infection can contribute to IP was provided by case studies and a placebo-controlled efficacy study of Helicobacter eradication. "Malignant" IP appears converted to "benign", but marked deterioration accompanies failure. Similar benefit on brady/hypokinesia from eradicating "low-density" infection favors autoimmunity. Although a minority of UK probands are urea breath test positive for Helicobacter , the predicted probability of having the parkinsonian label depends on the serum H. pylori antibody profile, with clinically relevant gradients between this "discriminant index" and disease burden and progression. In IP, H. pylori antibodies discriminate for persistently abnormal bowel function, and specific abnormal duodenal enterocyte mitochondrial morphology is described in relation to H. pylori infection. Slow intestinal transit manifests as constipation from the prodrome. Diarrhea may flag secondary small-intestinal bacterial overgrowth. This, coupled with genetically determined intense inflammatory response, might explain evolution from brady/hypokinetic to rigidity-predominant parkinsonism.  相似文献   
999.
Kinase inhibitors are a new class of therapeutics with a propensity to inhibit multiple targets. The biological consequences of multi-kinase activity are poorly defined, and an important step toward understanding the relationship between selectivity, efficacy and safety is the exploration of how inhibitors interact with the human kinome. We present interaction maps for 38 kinase inhibitors across a panel of 317 kinases representing >50% of the predicted human protein kinome. The data constitute the most comprehensive study of kinase inhibitor selectivity to date and reveal a wide diversity of interaction patterns. To enable a global analysis of the results, we introduce the concept of a selectivity score as a general tool to quantify and differentiate the observed interaction patterns. We further investigate the impact of panel size and find that small assay panels do not provide a robust measure of selectivity.  相似文献   
1000.
mRNA decapping is promoted by an RNA-binding channel in Dcp2   总被引:1,自引:0,他引:1  
Cap hydrolysis by Dcp2 is a critical step in several eukaryotic mRNA decay pathways. Processing requires access to cap-proximal nucleotides and the coordinated assembly of a decapping mRNP, but the mechanism of substrate recognition and regulation by protein interactions have remained elusive. Using NMR spectroscopy and kinetic analyses, we show that yeast Dcp2 resolves interactions with the cap and RNA body using a bipartite surface that forms a channel intersecting the catalytic and regulatory Dcp1-binding domains. The interaction with cap is weak but specific and requires binding of the RNA body to a dynamic interface. The catalytic step is stimulated by Dcp1 and its interaction domain, likely through a substrate-induced conformational change. Thus, activation of the decapping mRNP is restricted by access to 5'-proximal nucleotides, a feature that could act as a checkpoint in mRNA metabolism.  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