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   390篇
  免费   17篇
  2023年   3篇
  2022年   1篇
  2021年   4篇
  2020年   9篇
  2019年   11篇
  2018年   8篇
  2017年   9篇
  2016年   9篇
  2015年   17篇
  2014年   22篇
  2013年   31篇
  2012年   41篇
  2011年   28篇
  2010年   19篇
  2009年   21篇
  2008年   25篇
  2007年   19篇
  2006年   15篇
  2005年   24篇
  2004年   27篇
  2003年   6篇
  2002年   7篇
  2001年   8篇
  2000年   5篇
  1999年   7篇
  1998年   2篇
  1997年   4篇
  1996年   1篇
  1994年   1篇
  1993年   1篇
  1992年   5篇
  1991年   4篇
  1990年   2篇
  1989年   1篇
  1988年   1篇
  1987年   3篇
  1985年   1篇
  1984年   2篇
  1982年   1篇
  1979年   2篇
排序方式: 共有407条查询结果,搜索用时 31 毫秒
1.
One of the family of voltage-gated calcium channels (VGCC), the N-type Ca2+ channel, is located predominantly in neurons and is associated with a variety of neuronal responses, including neurodegeneration. A precise mechanism for how the N-type Ca2+ channel plays a role in neurodegenerative disease, however, is unknown. In this study, we immunized N-type Ca2+ channel α1B-deficient (α1B−/−) mice and their wild type (WT) littermates with myelin oligodendrocyte glycoprotein 35–55 and analyzed the progression of experimental autoimmune encephalomyelitis (EAE). The neurological symptoms of EAE in the α1B−/− mice were less severe than in the WT mice. In conjunction with these results, sections of the spinal cord (SC) from α1B−/− mice revealed a reduction in both leukocytic infiltration and demyelination compared with WT mice. No differences were observed in the delayed-type hypersensitivity response, spleen cell proliferation, or cytokine production from splenocytes between the two genotypes. On the other hand, Western blot array analysis and RT-PCR revealed that a typical increase in the expression of MCP-1 in the SC showed a good correlation with the infiltration of leukocytes into the SC. Likewise, immunohistochemical analysis showed that the predominant source of MCP-1 was activated microglia. The cytokine-induced production of MCP-1 in primary cultured microglia from WT mice was significantly higher than that from α1B−/− mice and was significantly inhibited by a selective N-type Ca2+ channel antagonist, ω-conotoxin GVIA or a withdrawal of extracellular Ca2+. These results suggest that the N-type Ca2+ channel is involved in the pathogenesis of EAE at least in part by regulating MCP-1 production by microglia.  相似文献   
2.
Phytomelatonin in the leaves and fruits of wild perennial plants   总被引:1,自引:0,他引:1  
Phytomelatonin has been documented in numerous flowering plants, mostly in cultivated species consumed by humans. Although frugivorous animals feed on fruits, the phytomelatonin content of these organs has hardly ever been tested in wild plants. The aim of this study was to determine the levels of phytomelatonin in the leaves and fleshy fruits of 31 wild perennial species known to be eaten by herbivorous and frugivorous mammals and birds. Considerable levels of phytomelatonin were found in the leaves of all the tested species, and some contained melatonin in their fruits as well. The melatonin content was found to vary significantly in different life forms (trees, shrubs, and climbers), with trees possessing the highest levels. The analysis revealed a significant positive correlation between the phytomelatonin levels in the leaves and the fruits of various species. However, the concentration found in the fruits was generally lower than that found in the leaves of the same species. Despite the presence of phytomelatonin in the fleshy fruits of different families, there was no noticeable common attribute among them. Phytomelatonin was exhibited in both the seeds and the pulp, with no obvious preference for either one. Although it was determined that ingested melatonin enters the bloodstream of birds and mammals, its specific role is still not certain. The potential impact of edible phytomelatonin on the circadian rhythm of herbivores and frugivores is discussed on the basis of these findings.  相似文献   
3.
Sex ratio theory has proved remarkably useful in testing theadaptive nature of animal behavior. A particularly productivearea in this respect is Hamilton's theory of local mate competition(LMC), which has been extended in numerous directions to includegreater biological realism, allowing more detailed tests inspecific organisms. We have presented one such extension, termedasymmetrical LMC, which occurs when egg laying by females ona patch is asynchronous, and emerging males do not disperse,resulting in the extent of LMC on a patch varying over time.Our aim here is to test whether the parasitoid wasp Nasoniavitripennis responds to variation in the degree of asymmetricalLMC. Specifically, we show that females adjust their offspringsex ratios in response to (1) variation in the amount of asynchronyin emergence between broods on a patch and (2) the number andproportion of previously parasitized hosts on the patch. Ourresults provide qualitative support for the predictions of theory,suggesting new levels of complexity in the sex ratio behaviorof this much-studied organism. However, our results do not alwaysprovide quantitative support for theory, suggesting furthercomplexities that must be clarified.  相似文献   
4.
Previous experimental studies of competition among foragers rarely distinguished between exploitation and interference competition. In many systems this separation is experimentally impossible without interfering with the natural behavior of the animals. Consequently, these studies can only demonstrate the combined effect of interference and exploitation on the forager’s feeding rate, namely, it usually decreases in a decelerating rate as a function of density. We suggest here a simple experimental and statistical procedure that facilitates the separation of the effects of interference from those of exploitation. This procedure includes manipulation of both predator density and the foraging experiment duration. The statistical analysis is based on multiple linear regression. The working assumption is that exploitation can be neglected at the beginning of the foraging experiment because, initially, predators do not experience diminishing returns in prey capture rates. Using both the results of an individual-based simulation and a field experiment dataset of gerbils foraging for seeds in an artificial food patch located in the field, we demonstrate that our procedure can successfully detect and separate the effect of interference from the combined overall effect of competition (i.e., interference plus exploitation). Inon Scharf and Ido Filin contributed equally to this paper.  相似文献   
5.
Models of cultural evolution study how the distribution of cultural traits changes over time. The dynamics of cultural evolution strongly depends on the way these traits are transmitted between individuals by social learning. Two prominent forms of social learning are payoff-based learning (imitating others that have higher payoffs) and conformist learning (imitating locally common behaviours). How payoff-based and conformist learning affect the cultural evolution of cooperation is currently a matter of lively debate, but few studies systematically analyse the interplay of these forms of social learning. Here we perform such a study by investigating how the interaction of payoff-based and conformist learning affects the outcome of cultural evolution in three social contexts. First, we develop a simple argument that provides insights into how the outcome of cultural evolution will change when more and more conformist learning is added to payoff-based learning. In a social dilemma (e.g. a Prisoner’s Dilemma), conformism can turn cooperation into a stable equilibrium; in an evasion game (e.g. a Hawk-Dove game or a Snowdrift game) conformism tends to destabilize the polymorphic equilibrium; and in a coordination game (e.g. a Stag Hunt game), conformism changes the basin of attraction of the two equilibria. Second, we analyse a stochastic event-based model, revealing that conformism increases the speed of cultural evolution towards pure equilibria. Individual-based simulations as well as the analysis of the diffusion approximation of the stochastic model by and large confirm our findings. Third, we investigate the effect of an increasing degree of conformism on cultural group selection in a group-structured population. We conclude that, in contrast to statements in the literature, conformism hinders rather than promotes the evolution of cooperation.  相似文献   
6.
The interactions of cells with basement membranes are primarily mediated via the engagement of laminins by a group of integrin family proteins, including integrins alpha3beta1, alpha6beta1, alpha7beta1 and alpha6beta4. To explore the ligand-binding specificities of these laminin-binding integrins, we produced these integrins, including two alpha7beta1 splice variants (alpha7X1beta1 and alpha7X2beta1), as soluble recombinant proteins and determined their binding specificities and affinities toward a panel of purified laminin isoforms containing distinct alpha chains. Among the five laminin-binding integrins investigated, alpha3beta1 and alpha6beta4 exhibited a clear specificity for laminin-332 (alpha3beta3gamma2) and laminin-511 (alpha5beta1gamma1)/521 (alpha5beta2gamma1), while integrin alpha6beta1 showed a broad specificity, binding to all laminin isoforms with a preference for laminin-111 (alpha1beta1gamma1), laminin-332 and laminin-511/521. The two alpha7beta1 variants were distinct from alpha3beta1, alpha6beta1 and alpha6beta4 in that they did not bind to laminin-332. alpha7X1beta1 bound to all laminins, except laminin-332, with a preference for laminin-211 (alpha2beta1gamma1)/221 (alpha2beta2gamma1) and laminin-511/521, while alpha7X2beta1 bound preferentially to laminin-111 and laminin-211/221. Laminin-511/521 was the most preferred ligand for all the laminin-binding integrins, except for alpha7X2beta1, whereas laminin-411 was the poorest ligand, capable of binding to alpha6beta1 and alpha7X1beta1 with only modest binding affinities. These comprehensive analyses of the interactions between laminin-binding integrins and a panel of laminins clearly demonstrate that the isoforms of both integrins and laminins differ in their binding specificities and affinities, and provide a molecular basis for better understanding of the adhesive interactions of cells with basement membranes of defined laminin compositions.  相似文献   
7.
The phyllosphere is one of the largest habitats for terrestrial microorganisms. To gain a better insight into the factors underlying the composition of bacterial communities inhabiting leaf surfaces we performed culture-dependent and independent (Denaturing Gradient Gel Electrophoresis) analyses on the bacteria associated with the leaves of three plant species: Amygdalus communis, Citrus paradisi, and Nicotiana glauca. We found that the culturable classes Bacilli and Actinobacteria were the predominant classes on the phyllosphere of all three plant species. In contrast to this consistency on the bacterial class level, we found a significant variation on the bacterial species-level based on the culturable methods. Although some variation was detected among individual plants within one plant species, the inter-specific variability exceeded the intra-specific variability. C. paradisi leaf surface had the highest predicted total species richness (Chao 2 and ICE) and the highest species diversity (βw) among the three plant species. Our findings demonstrate that environmental conditions, mainly the plant species within a site, govern the bacterial community composition on leaf surfaces.  相似文献   
8.
Sex allocation theory predicts the optimal allocation to male and female reproduction in sexual organisms. In animals, most work on sex allocation has focused on species with separate sexes and our understanding of simultaneous hermaphrodites is patchier. Recent theory predicts that sex allocation in simultaneous hermaphrodites should strongly be affected by post-copulatory sexual selection, while the role of pre-copulatory sexual selection is much less clear. Here, we review sex allocation and sexual selection theory for simultaneous hermaphrodites, and identify several strong and potentially unwarranted assumptions. We then present a model that treats allocation to sexually selected traits as components of sex allocation and explore patterns of allocation when some of these assumptions are relaxed. For example, when investment into a male sexually selected trait leads to skews in sperm competition, causing local sperm competition, this is expected to lead to a reduced allocation to sperm production. We conclude that understanding the evolution of sex allocation in simultaneous hermaphrodites requires detailed knowledge of the different sexual selection processes and their relative importance. However, little is currently known quantitatively about sexual selection in simultaneous hermaphrodites, about what the underlying traits are, and about what drives and constrains their evolution. Future work should therefore aim at quantifying sexual selection and identifying the underlying traits along the pre- to post-copulatory axis.  相似文献   
9.
Aggregation of TAR DNA-binding protein of 43 kDa (TDP-43) is a pathological signature of amyotrophic lateral sclerosis (ALS). Although accumulating evidence suggests the involvement of RNA recognition motifs (RRMs) in TDP-43 proteinopathy, it remains unclear how native TDP-43 is converted to pathogenic forms. To elucidate the role of homeostasis of RRM1 structure in ALS pathogenesis, conformations of RRM1 under high pressure were monitored by NMR. We first found that RRM1 was prone to aggregation and had three regions showing stable chemical shifts during misfolding. Moreover, mass spectrometric analysis of aggregated RRM1 revealed that one of the regions was located on protease-resistant β-strands containing two cysteines (Cys-173 and Cys-175), indicating that this region served as a core assembly interface in RRM1 aggregation. Although a fraction of RRM1 aggregates comprised disulfide-bonded oligomers, the substitution of cysteine(s) to serine(s) (C/S) resulted in unexpected acceleration of amyloid fibrils of RRM1 and disulfide-independent aggregate formation of full-length TDP-43. Notably, TDP-43 aggregates with RRM1-C/S required the C terminus, and replicated cytopathologies of ALS, including mislocalization, impaired RNA splicing, ubiquitination, phosphorylation, and motor neuron toxicity. Furthermore, RRM1-C/S accentuated inclusions of familial ALS-linked TDP-43 mutants in the C terminus. The relevance of RRM1-C/S-induced TDP-43 aggregates in ALS pathogenesis was verified by immunolabeling of inclusions of ALS patients and cultured cells overexpressing the RRM1-C/S TDP-43 with antibody targeting misfolding-relevant regions. Our results indicate that cysteines in RRM1 crucially govern the conformation of TDP-43, and aberrant self-assembly of RRM1 at amyloidogenic regions contributes to pathogenic conversion of TDP-43 in ALS.  相似文献   
10.
Mutations in the p53 tumor suppressor protein are highly frequent in tumors and often endow cells with tumorigenic capacities. We sought to examine a possible role for mutant p53 in the cross-talk between cancer cells and their surrounding stroma, which is a crucial factor affecting tumor outcome. Here we present a novel model which enables individual monitoring of the response of cancer cells and stromal cells (fibroblasts) to co-culturing. We found that fibroblasts elicit the interferon beta (IFNβ) pathway when in contact with cancer cells, thereby inhibiting their migration. Mutant p53 in the tumor was able to alleviate this response via SOCS1 mediated inhibition of STAT1 phosphorylation. IFNβ on the other hand, reduced mutant p53 RNA levels by restricting its RNA stabilizer, WIG1. These data underscore mutant p53 oncogenic properties in the context of the tumor microenvironment and suggest that mutant p53 positive cancer patients might benefit from IFNβ treatment.  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