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   2164篇
  免费   191篇
  2024年   1篇
  2023年   7篇
  2022年   28篇
  2021年   41篇
  2020年   31篇
  2019年   34篇
  2018年   57篇
  2017年   38篇
  2016年   78篇
  2015年   133篇
  2014年   159篇
  2013年   157篇
  2012年   224篇
  2011年   212篇
  2010年   106篇
  2009年   111篇
  2008年   159篇
  2007年   151篇
  2006年   121篇
  2005年   125篇
  2004年   98篇
  2003年   90篇
  2002年   80篇
  2001年   11篇
  2000年   9篇
  1999年   14篇
  1998年   20篇
  1997年   22篇
  1996年   8篇
  1995年   10篇
  1994年   2篇
  1993年   1篇
  1992年   5篇
  1991年   2篇
  1990年   4篇
  1989年   1篇
  1984年   1篇
  1983年   1篇
  1978年   1篇
  1977年   1篇
  1974年   1篇
排序方式: 共有2355条查询结果,搜索用时 156 毫秒
51.
Various nonhuman primate species have been tested with prosocial games (i.e. derivates from dictator games) in order to better understand the evolutionary origin of proactive prosociality in humans. Results of these efforts are mixed, and it is difficult to disentangle true species differences from methodological artifacts. We tested 2- to 5-year-old children with a costly and a cost-free version of a prosocial game that differ with regard to the payoff distribution and are widely used with nonhuman primates. Simultaneously, we assessed the subjects’ level of Theory of Mind understanding. Prosocial behavior was demonstrated with the prosocial game, and did not increase with more advanced Theory of Mind understanding. However, prosocial behavior could only be detected with the costly version of the game, whereas the children failed the cost-free version that is most commonly used with nonhuman primates. A detailed comparison of the children’s behavior in the two versions of the game indicates that the failure was due to higher attentional demands of the cost-free version, rather than to a lack of prosociality per se. Our results thus show (i) that subtle differences in prosociality tasks can substantially bias the outcome and thus prevent meaningful species comparisons, and (ii) that like in nonhuman primates, prosocial behavior in human children does not require advanced Theory of Mind understanding in the present context. However, both developmental and comparative psychology accumulate increasing evidence for the multidimensionality of prosocial behaviors, suggesting that different forms of prosociality are also regulated differentially. For future efforts to understand the evolutionary origin of prosociality it is thus crucial to take this heterogeneity into account.  相似文献   
52.
Antibiotic resistance has been reported since the introduction of synthetic antibiotics. Bacteria, such as one of the most common nosocomial pathogens P. aeruginosa, adapt quickly to changing environmental conditions, due to their short generation time. Thus microevolutional changes can be monitored in situ. In this study, the microevolutional process of Pseudomonas aeruginosa PAO1 resistance against a recently developed novel antibacterial zinc Schiff-base (ZSB) was investigated at the proteome level. After extended exposure to ZSB the passaged strain differed in tolerance against ZSB, with the adapted P. aeruginosa PAO1 exhibiting 1.6 times higher minimal inhibitory concentration. Using Two-dimensional Difference Gel Electrophoresis, the changes in the proteome of ZSB adapted P. aeruginosa PAO1 were examined by comparison with the non-adapted P. aeruginosa PAO1. The proteome of the adapted P. aeruginosa PAO1 strain differed significantly from the non-adapted in the abundance of two proteins when both strains were grown under stressing conditions. One protein could be identified as the outer membrane protein D that plays a role in uptake of basic amino acids as well as in carbapeneme resistance. The second protein has been identified as alkyl peroxide reductase subunit F. Our data indicated a slight increase in abundance of alkyl peroxide reductase F (AhpF) in the case of ZSB passaged P. aeruginosa PAO1. Higher abundance of Ahp has been discussed in the literature as a promoter of accelerated detoxification of benzene derivatives. The observed up-regulated AhpF thus appears to be connected to an increased tolerance against ZSB. Changes in the abundance of proteins connected to oxidative stress were also found after short-time exposure of P. aeruginosa PAO1 to the ZSB. Furthermore, adapted P. aeruginosa PAO1 showed increased tolerance against hydrogen peroxide and, in addition, showed accelerated degradation of ZSB, as determined by HPLC measurements.  相似文献   
53.
The scabies mite, Sarcoptes scabiei, is an obligate parasite of the skin that infects humans and other animal species, causing scabies, a contagious disease characterized by extreme itching. Scabies infections are a major health problem, particularly in remote Indigenous communities in Australia, where co-infection of epidermal scabies lesions by Group A Streptococci or Staphylococcus aureus is thought to be responsible for the high rate of rheumatic heart disease and chronic kidney disease. We collected and separately sequenced mite DNA from several pools of thousands of whole mites from a porcine model of scabies (S. scabiei var. suis) and two human patients (S. scabiei var. hominis) living in different regions of northern Australia. Our sequencing samples the mite and its metagenome, including the mite gut flora and the wound micro-environment. Here, we describe the mitochondrial genome of the scabies mite. We developed a new de novo assembly pipeline based on a bait-and-reassemble strategy, which produced a 14 kilobase mitochondrial genome sequence assembly. We also annotated 35 genes and have compared these to other Acari mites. We identified single nucleotide polymorphisms (SNPs) and used these to infer the presence of six haplogroups in our samples, Remarkably, these fall into two closely-related clades with one clade including both human and pig varieties. This supports earlier findings that only limited genetic differences may separate some human and animal varieties, and raises the possibility of cross-host infections. Finally, we used these mitochondrial haplotypes to show that the genetic diversity of individual infections is typically small with 1–3 distinct haplotypes per infestation.  相似文献   
54.
BackgroundAntenatal depression affects up to 19% of pregnant women. Some of these women are also in need of antidepressant treatment. Nevertheless, the impact of maternal antidepressant treatment and prenatal depression on the course of pregnancy, foetal development and delivery outcomes is not fully understood.MethodsWe analysed data from 24 818 women who gave birth at Kuopio University Hospital between 2002–2012. Logistic regression analysis was used to estimate associations between the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy and the progression of pregnancy, development of the foetus and delivery outcomes.ResultsAltogether, 369 (1.5%) women used SSRIs. A regression model adjusted for age, overweight, nulliparity, prior termination, miscarriages, smoking, maternal alcohol consumption, chronic illness and polyhydramnion showed that pregnant women exposed to SSRI medication had significantly lower Apgar scores at 1 minute (p < 0.0001) and 5 minutes (p < 0.0001) and more admissions to the neonatal intensive care unit (p < 0.0001) than unexposed pregnant women. In addition, exposed newborns had longer umbilical cords (p < 0.0001) than non-exposed newborns.ConclusionIn addition to the previously known associates with maternal SSRI exposure, such as lowered Apgar scores, SSRI exposure appeared to be associated with increased umbilical cord length. The observation related to increased umbilical cord length may be explained by an SSRI-induced increase in the movements of the developing foetus.  相似文献   
55.
Investigating how interactions among plants depend on environmental conditions is key to understand and predict plant communities’ response to climate change. However, while many studies have shown how direct interactions change along climatic gradients, indirect interactions have received far less attention. In this study, we aim at contributing to a more complete understanding of how biotic interactions are modulated by climatic conditions. We investigated both direct and indirect effects of adult tree canopy and ground vegetation on seedling growth and survival in five tree species in the French Alps. To explore the effect of environmental conditions, the experiment was carried out at 10 sites along a climatic gradient closely related to temperature. While seedling growth was little affected by direct and indirect interactions, seedling survival showed significant patterns across multiple species. Ground vegetation had a strong direct competitive effect on seedling survival under warmer conditions. This effect decreased or shifted to facilitation at lower temperatures. While the confidence intervals were wider for the effect of adult canopy, it displayed the same pattern. The monitoring of micro‐environmental conditions revealed that competition by ground vegetation in warmer sites could be related to reduced water availability; and weak facilitation by adult canopy in colder sites to protection against frost. For a cold‐intolerant and shade‐tolerant species (Fagus sylvatica), adult canopy indirectly facilitated seedling survival by suppressing ground vegetation at high temperature sites. The other more cold tolerant species did not show this indirect effect (Pinus uncinata, Larix decidua and Abies alba). Our results support the widely observed pattern of stronger direct competition in more productive climates. However, for shade tolerant species, the effect of direct competition may be buffered by tree canopies reducing the competition of ground vegetation, resulting in an opposite trend for indirect interactions across the climatic gradient.  相似文献   
56.
57.
58.
RING‐in‐between‐RING (RBR) ubiquitin (Ub) ligases are a distinct class of E3s, defined by a RING1 domain that binds E2 Ub‐conjugating enzyme and a RING2 domain that contains an active site cysteine similar to HECT‐type E3s. Proposed to function as RING/HECT hybrids, details regarding the Ub transfer mechanism used by RBRs have yet to be defined. When paired with RING‐type E3s, E2s perform the final step of Ub ligation to a substrate. In contrast, when paired with RBR E3s, E2s must transfer Ub onto the E3 to generate a E3~Ub intermediate. We show that RBRs utilize two strategies to ensure transfer of Ub from the E2 onto the E3 active site. First, RING1 domains of HHARI and RNF144 promote open E2~Ubs. Second, we identify a Ub‐binding site on HHARI RING2 important for its recruitment to RING1‐bound E2~Ub. Mutations that ablate Ub binding to HHARI RING2 also decrease RBR ligase activity, consistent with RING2 recruitment being a critical step for the RBR Ub transfer mechanism. Finally, we demonstrate that the mechanism defined here is utilized by a variety of RBRs.  相似文献   
59.

Introduction

Human primary cells originating from different locations within the body could differ greatly in their metabolic phenotypes, influencing both how they act during physiological/pathological processes and how susceptible/resistant they are to a variety of disease risk factors. A novel way to monitor cellular metabolism is through cell energetics assays, so we explored this approach with human primary cell types, as models of sclerotic disorders.

Objectives

In order to better understand pathophysiological processes at the cellular level, our goals were to measure metabolic pathway activities of endothelial cells and fibroblasts, and determine their metabolic phenotype profiles.

Methods

Biolog Phenotype MicroArray? technology was used for the first time to characterize metabolic phenotypes of diverse primary cells. These colorimetric assays enable detection of utilization of 367 specific biochemical substrates by human endothelial cells from the coronary artery (HCAEC), umbilical vein (HUVEC) and normal, healthy lung fibroblasts (NHLF).

Results

Adenosine, inosine, d-mannose and dextrin were strongly utilized by all three cell types, comparable to glucose. Substrates metabolized solely by HCAEC were mannan, pectin, gelatin and prevalently tricarballylic acid. HUVEC did not show any uniquely metabolized substrates whereas NHLF exhibited strong utilization of sugars and carboxylic acids along with amino acids and peptides.

Conclusion

Taken together, we show for the first time that this simple energetics assay platform enables metabolic characterization of primary cells and that each of the three human cell types examined gives a unique and distinguishable profile.
  相似文献   
60.
Experimental evolution (EE) is a powerful tool for addressing how environmental factors influence life‐history evolution. While in nature different selection pressures experienced across the lifespan shape life histories, EE studies typically apply selection pressures one at a time. Here, we assess the consequences of adaptation to three different developmental diets in combination with classical selection for early or late reproduction in the fruit fly Drosophila melanogaster. We find that the response to each selection pressure is similar to that observed when they are applied independently, but the overall magnitude of the response depends on the selection regime experienced in the other life stage. For example, adaptation to increased age at reproduction increased lifespan across all diets; however, the extent of the increase was dependent on the dietary selection regime. Similarly, adaptation to a lower calorie developmental diet led to faster development and decreased adult weight, but the magnitude of the response was dependent on the age‐at‐reproduction selection regime. Given that multiple selection pressures are prevalent in nature, our findings suggest that trade‐offs should be considered not only among traits within an organism, but also among adaptive responses to different—sometimes conflicting—selection pressures, including across life stages.  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