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目的

探索肠道菌群缺失对紫杉醇诱导的神经病理性疼痛行为的影响及相关机制。

方法

32只C57雄性小鼠随机分为4组(n=8):对照组(Control组)、抗生素组(ASC组)、紫杉醇组(PTX组)和抗生素+紫杉醇组(PTX+ASC组)。紫杉醇造模前,抗生素组小鼠口服ASC三联广谱抗生素(1 mg/mL),持续2周。第1、3、5、7天腹腔注射紫杉醇(2 mg/kg)建立神经病理性疼痛模型。紫杉醇给药前和给药后第14天分别测定小鼠的热缩足潜伏期(TWL)和机械缩足反应阈(MWT)。行为学实验结束后,取小鼠粪便样本(5~6粒/只)用于16S rRNA扩增子测序分析。Western blot法检测小鼠脊髓水平Toll样受体4(TLR4)蛋白和核因子κB(NF-κB)蛋白的表达情况。免疫荧光检测脊髓星形胶质细胞的活化情况。ELISA实验检测脊髓内肿瘤坏死因子α(TNF-α)和白细胞介素−1β(IL-1β)的表达水平。

结果

与对照组相比,口服ASC抗生素的小鼠,肠道菌群在科水平上Muribaculaceae、乳杆菌科和阿克曼菌科相对丰度显著下降(P<0.05);紫杉醇2 mg/kg造模后,小鼠机械/热痛阈值显著下降(P<0.05),小鼠脊髓TLR4和NF-κB蛋白和促炎性因子TNF-α、IL-1β表达水平显著升高(P<0.05),脊髓星形胶质细胞异常活化(P<0.05)。与紫杉醇组相比,抗生素+紫杉醇组小鼠的机械/热痛阈值显著升高(P<0.05)。小鼠脊髓内TLR4和NF-κB蛋白和TNF-α、IL-1β的表达显著降低(P<0.05),星形胶质细胞活化水平显著减弱(P<0.05)。

结论

ASC抗生素三联给药造成的肠道菌群缺失可缓解紫杉醇诱导的小鼠神经病理性疼痛,并可抑制紫杉醇诱导的脊髓TLR4/NF-κB信号通路蛋白的过表达,星形胶质细胞活化和炎性反应。

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Using two genetic approaches and seven different plant systems, we present findings from a meta-analysis examining the strength of the effects of plant genetic introgression and genotypic diversity across individual, community and ecosystem levels with the goal of synthesizing the patterns to date. We found that (i) the strength of plant genetic effects can be quite high; however, the overall strength of genetic effects on most response variables declined as the levels of organization increased. (ii) Plant genetic effects varied such that introgression had a greater impact on individual phenotypes than extended effects on arthropods or microbes/fungi. By contrast, the greatest effects of genotypic diversity were on arthropods. (iii) Plant genetic effects were greater on above-ground versus below-ground processes, but there was no difference between terrestrial and aquatic environments. (iv) The strength of the effects of intraspecific genotypic diversity tended to be weaker than interspecific genetic introgression. (v) Although genetic effects generally decline across levels of organization, in some cases they do not, suggesting that specific organisms and/or processes may respond more than others to underlying genetic variation. Because patterns in the overall impacts of introgression and genotypic diversity were generally consistent across diverse study systems and consistent with theoretical expectations, these results provide generality for understanding the extended consequences of plant genetic variation across levels of organization, with evolutionary implications.  相似文献   
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Antibodies provide a sensitive indicator of proteins displayed by bacteria during sepsis. Because signals produced by infection are naturally amplified during the antibody response, host immunity can be used to identify biomarkers for proteins that are present at levels currently below detectable limits. We developed a microarray comprising ∼70% of the 4066 proteins contained within the Yersinia pestis proteome to identify antibody biomarkers distinguishing plague from infections caused by other bacterial pathogens that may initially present similar clinical symptoms. We first examined rabbit antibodies produced against proteomes extracted from Y. pestis, Burkholderia mallei, Burkholderia cepecia, Burkholderia pseudomallei, Pseudomonas aeruginosa, Salmonella typhimurium, Shigella flexneri, and Escherichia coli, all pathogenic Gram-negative bacteria. These antibodies enabled detection of shared cross-reactive proteins, fingerprint proteins common for two or more bacteria, and signature proteins specific to each pathogen. Recognition by rabbit and non-human primate antibodies involved less than 100 of the thousands of proteins present within the Y. pestis proteome. Further antigen binding patterns were revealed that could distinguish plague from anthrax, caused by the Gram-positive bacterium Bacillus anthracis, using sera from acutely infected or convalescent primates. Thus, our results demonstrate potential biomarkers that are either specific to one strain or common to several species of pathogenic bacteria.Plague is a disease of historical epidemics that remains an important public health problem in limited areas of the world (1). Disease transmission usually occurs through transfer of the bacillus Yersinia pestis by the bite of a flea. However, less frequent direct transfer of viable bacteria by respiratory droplets may result in primary pneumonic infection. A transient intracellular infection of phagocytic cells (2) occurs during the earliest stage of bubonic plague followed by rapid extracellular expansion of bacteria in lymph nodes. The prototypical lymphatic infection of bubonic plague may also progress to bacteremic or pneumonic infection with a very high rate of fatality if there is not rapid intervention by antibiotic treatment (3). Among the reported cases occurring annually in the United States, 15% were fatal in 2006 (4). Although only small numbers of human cases occur each year in North America, a more substantial incidence of plague is found in wild animal populations (5) with seroprevalence rates of up to 100% among mammalian carnivores in endemic areas (6). The geographic range of infection within feral populations is presently unknown but may contribute significantly to the reservoir of potential disease transmission to humans.Diagnostic tests and prophylactic vaccines or therapies must rapidly distinguish or protect against the many infectious diseases that present similar initial symptoms. Specific diagnostic tests and vaccines for plague are public health priorities primarily because of the threat from potential acts of terrorism. Because human deaths may occur within 48 h of infection (7), delays in proper diagnosis have led to disease complications and fatalities from plague (8). Yet the identification of bacterial sepsis at the earliest stage of clinical presentation is challenging because of the generalized nature of disease symptoms and the difficulty in culturing infectious agents or isolating sufficient material to identify the infectious agent by amplification of genetic markers. Although host antibody responses provide a sensitive indicator of current or past infection, insufficient numbers of validated biomarkers are available, and extensive antibody cross-reactivity among Gram-negative pathogens (912) complicates the direct analysis of serum.Identification of plague-specific antibody interactions is a daunting task because of the complexity of the bacterial proteome encountered by the host during infection. The chromosome of Y. pestis CO92 encodes ∼3885 proteins, whereas an additional 181 are episomally expressed by pCD1, pMT1, and pPCP1. For comparison, the proteome of Y. pestis KIM1 contains 4202 individual proteins (13), 87% in common with CO92 (14), and the closely related enteric pathogen Yersinia pseudotuberculosis (15, 16) contains ∼4038 proteins (chromosome plus plasmids). Recent technical advances have facilitated the development of microarrays comprising full-length, functional proteins that represent nearly complete proteomes. For example, Zhu et al. (17) reported the development of a proteome microarray containing the full-length, purified expression products of over 93% of the 6280 protein-coding genes of the yeast Saccharomyces cerevisiae, and Schmid et al. (18) described the human antibody repertoire for vaccinia virus recognition by using a viral proteome microarray. This approach opens the possibility of examining the entire bacterial proteome to elucidate proteins or protein pathways that are essential to pathogenicity or host immunity. We sought to identify biomarkers that could distinguish plague from diseases caused by other bacterial pathogens by measuring host antibody recognition of individual proteins contained within the Y. pestis proteome. The previously reported genomic sequences of Y. pestis strains KIM (13) and CO92 (14), sharing 95% identity, were used for reference. Approximately 77% of the putative Y. pestis proteome can be classified by known homologies. We successfully expressed and purified the majority (70%) of the 4066 ORFs encoded by the chromosome and plasmids of Y. pestis KIM and arrayed these products onto glass slides coated with nitrocellulose. The Y. pestis ORFs subcloned into expression vectors were fully sequenced to confirm quality and identity before use. Different approaches for studying the antibody repertoire for plague in rabbits and non-human primates were compared. Based on results from experiments using the Y. pestis proteome microarray, we identified new candidates for antibody biomarkers of bacterial infections and patterns of cross-reactivity that may be useful diagnostic tools.  相似文献   
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Transformation and loss of natural habitat to urbanization and agriculture provide new opportunities for primates to feed on anthropogenic food sources. Currently, mitigation strategies fail to target the individuals responsible for initiating and maintaining this behavior. As primates mainly forage on crops in groups, we investigate the crop-foraging behavior of a group of 40 chacma baboons in Zimbabwe from the perspective of collective movements, i.e., when a group of animals move together in the same direction, thus resulting in a change of location. We collected data on 110 crop-foraging events during 35 days in March–April 2014. We recorded baboon movement and behavior with a camcorder and obtained further information through video analysis. Most crop-foraging events involved less than 20% of the troop and lasted less than 3 min. Although crop-foraging parties were composed of all age–sex classes, adult females and particularly adult males initiated most crop-foraging events and made direct movements (without stopping on the road) more often than nonadult participants. Baboons made up to five successive attempts to crop forage in a single crop-foraging event. Neither the number of participants nor the success of the crop-foraging events increased over the successive attempts. Finally, crop-foraging events were more successful and more frequent in unguarded areas than in guarded areas. These results suggest that group members are highly synchronized and that crop-foraging is based on a collective decision such as classical foraging movements. In addition, the short duration of the crop-foraging events might prevent detection of baboons by farmers. The more frequent initiation of crop-foraging by adults compared to nonadults might be explained by greater energetic needs or a greater tendency of adults to take risks. These preliminary data can help inform long-term strategies for farmers to reduce crop losses to baboons, as guarding helps reduce damage but does not prevent it.  相似文献   
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辽宁是东北林蛙Rana dybowskii主要分布地之一,种群数量巨大,其群体遗传多样性有待评估.本研究应用ISSR标记技术对东北林蛙4个种群105个样本进行研究,5个引物共获得44条清晰谱带,4个种群的多态位点率均大于75%,Nei's基因多样性为0.2851,Shannon信息指数为0.4476,显示了较高的遗传多样性.对遗传分化系数、Nei's遗传距离、AMOVA分子变异巢式方差分析和F-统计量等遗传参数的统计结果表明,辽宁东北林蛙种群间已经出现一定程度的遗传分化,分析认为,自然屏障(高山和平原等)以及栖息地片段化是其遗传分化形成的主要因素.  相似文献   
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Re-examination, using molecular tools, of the diversity of haemosporidian parasites (among which the agents of human malaria are the best known) has generally led to rearrangements of traditional classifications. In this study, we explored the diversity of haemosporidian parasites infecting vertebrate species (particularly mammals, birds and reptiles) living in the forests of Gabon (Central Africa), by analyzing a collection of 492 bushmeat samples. We found that samples from five mammalian species (four duiker and one pangolin species), one bird and one turtle species were infected by haemosporidian parasites. In duikers (from which most of the infected specimens were obtained), we demonstrated the existence of at least two distinct parasite lineages related to Polychromophilus species (i.e., bat haemosporidian parasites) and to sauropsid Plasmodium (from birds and lizards). Molecular screening of sylvatic mosquitoes captured during a longitudinal survey revealed the presence of these haemosporidian parasite lineages also in several Anopheles species, suggesting a potential role in their transmission. Our results show that, differently from what was previously thought, several independent clades of haemosporidian parasites (family Plasmodiidae) infect mammals and are transmitted by anopheline mosquitoes.  相似文献   
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Out of all the complex phenomena displayed in the behaviour of animal groups, many are thought to be emergent properties of rather simple decisions at the individual level. Some of these phenomena may also be explained by random processes only. Here we investigate to what extent the interaction dynamics of a population of wild house mice (Mus domesticus) in their natural environment can be explained by a simple stochastic model. We first introduce the notion of perceptual landscape, a novel tool used here to describe the utilisation of space by the mouse colony based on the sampling of individuals in discrete locations. We then implement the behavioural assumptions of the perceptual landscape in a multi-agent simulation to verify their accuracy in the reproduction of observed social patterns. We find that many high-level features – with the exception of territoriality – of our behavioural dataset can be accounted for at the population level through the use of this simplified representation. Our findings underline the potential importance of random factors in the apparent complexity of the mice''s social structure. These results resonate in the general context of adaptive behaviour versus elementary environmental interactions.  相似文献   
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