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   1053篇
  免费   53篇
  1106篇
  2023年   6篇
  2022年   20篇
  2021年   35篇
  2020年   18篇
  2019年   25篇
  2018年   34篇
  2017年   33篇
  2016年   37篇
  2015年   49篇
  2014年   80篇
  2013年   68篇
  2012年   98篇
  2011年   101篇
  2010年   46篇
  2009年   41篇
  2008年   47篇
  2007年   53篇
  2006年   51篇
  2005年   51篇
  2004年   35篇
  2003年   31篇
  2002年   28篇
  2001年   5篇
  2000年   7篇
  1999年   9篇
  1998年   5篇
  1997年   4篇
  1995年   4篇
  1994年   4篇
  1993年   4篇
  1990年   3篇
  1989年   3篇
  1988年   6篇
  1985年   4篇
  1984年   2篇
  1983年   6篇
  1981年   2篇
  1980年   3篇
  1979年   4篇
  1978年   5篇
  1977年   4篇
  1976年   4篇
  1975年   2篇
  1974年   2篇
  1973年   2篇
  1969年   2篇
  1967年   3篇
  1966年   5篇
  1959年   2篇
  1957年   2篇
排序方式: 共有1106条查询结果,搜索用时 0 毫秒
121.
122.
Guided by the social emotional learning framework, this study examined whether early adolescents’ social awareness (empathic concern, perspective taking) and self-management (effortful control) would uniquely contribute to early adolescents’ subsequent forms of aggression, and whether perceptions of their school climate (friction, cohesion, competition, satisfaction with classes) would moderate those associations. Participants were 479 10- to 14-year old students (54% female; 78% European American) who completed the first wave of a survey in sixth and seventh grades and the second wave 1 year later. Hierarchical regression analyses indicated that across gender, empathic concern was the only competency to reduce subsequent overt and relational aggression. None of the school climate perceptions made unique contributions to aggression, nor did they show protective functions. Rather, several instances of cumulative advantage were observed, whereby positive school climate perceptions only reduced aggression for students with high levels of empathic concern. Unexpectedly, boys’ perceived cohesion contributed to overt aggression if they reported high levels of effortful control.  相似文献   
123.
124.
Solidago gigantea Ait. (goldenrod) belongs to the most expansive environmental weeds, and it is the most dangerous plant-invader of American origin in Europe. The species easily propagates vegetatively, but it also produces large amounts of wind-disseminated achenes that contribute to the colonization of new areas. A sound knowledge of the germination biology of goldenrods is required to control the spread of this invasive species. The objective of this study was to investigate selected aspects of germination of giant goldenrod achenes and to determine: the influence of temperature and humidity on seed dormancy and germination, the content of soluble carbohydrates in seeds and the sensitivity of seeds to selected phytohormones. Unlike native weed species of the same family, S. gigantea seeds did not display symptoms of innate dormancy, and high seed vigor was maintained after storage in a wide range of temperatures, in both dry and moist conditions. The physiological mechanisms behind those traits have not yet been fully explored, but they could be associated with the relatively high sucrose-to-hexose ratio in seeds and significant sensitivity to abscisic acid. More extensive research is required to explain the internal causes for the atypical behavior of goldenrod seeds during dry and moist storage, especially in the context of its invasiveness, because the species has a preference for sites located close to river banks.  相似文献   
125.
Biological membranes are organized into dynamic microdomains that serve as sites for signal transduction and membrane trafficking. The formation and expansion of these microdomains are driven by intrinsic properties of membrane lipids and integral as well as membrane-associated proteins. Annexin A2 (AnxA2) is a peripherally associated membrane protein that can support microdomain formation in a Ca2+-dependent manner and has been implicated in membrane transport processes. Here, we performed a quantitative analysis of the binding of AnxA2 to solid supported membranes containing the annexin binding lipids phosphatidylinositol-4,5-bisphosphate and phosphatidylserine in different compositions. We show that the binding is of high specificity and affinity with dissociation constants ranging between 22.1 and 32.2 nM. We also analyzed binding parameters of a heterotetrameric complex of AnxA2 with its S100A10 protein ligand and show that this complex has a higher affinity for the same membranes with Kd values of 12 to 16.4 nM. Interestingly, binding of the monomeric AnxA2 and the AnxA2-S100A10 complex are characterized by positive cooperativity. This cooperative binding is mediated by the conserved C-terminal annexin core domain of the protein and requires the presence of cholesterol. Together our results reveal for the first time, to our knowledge, that AnxA2 and its derivatives bind cooperatively to membranes containing cholesterol, phosphatidylserine, and/or phosphatidylinositol-4,5-bisphosphate, thus providing a mechanistic model for the lipid clustering activity of AnxA2.  相似文献   
126.
Apoptotic death of CD4+ T lymphocytes is a major cause of the immunodeficiency caused by human immunodeficiency virus (HIV), but it is still unclear how this process precisely occurs. To characterize a potentially useful cellular model, we have analyzed the tendency of chronically HIV-infected CD4+ human cell lines of different origin to undergo apoptosis. We studied ACH-2 and U1 lines, derived from the CD4+ T-cell A301 and the promonocytic U937 cell lines, respectively, and induced apoptosis via several stimuli that trigger different pathways. Their capacity to regulate plasma membrane CD95 expression and to produce soluble CD95 was also analyzed. Using staurosporine, TNF-alpha plus cycloheximide, and gamma-radiations, we observed that ACH-2 were more sensitive to programmed cell death than A301, while U1 were less sensitive than U937. Both infected cell types had a lower sensitivity to CD95-induced apoptosis; the analysis of changes in mitochondrial membrane potential corroborated these observations. Plasma membrane CD95 was similarly regulated in all cell types, which, however, presented a different capacity to produce soluble CD95 molecules. Our in vitro results may offer a new perspective for developing further studies on the pathogenesis of HIV infection. A chronically infected cell line of lymphocytic origin is more susceptible to apoptosis than its parental cell type, while infected monocytic cells are less sensitive than their uninfected counterpart. Thus, it is possible to hypothesize that one of the reasons by which circulating monocytes survive and represent a viral reservoir is the capacity of HIV to decrease the sensitivity to apoptosis of this cell type. However, further studies on ex-vivo collected fresh cells, as well as on other cell lines, are urgently needed to confirm such hypothesis.  相似文献   
127.
Precise coordination of protein biogenesis, traffic and homeostasis within the early secretory compartment (ESC) is key for cell physiology. As a consequence, disturbances in these processes underlie many genetic and chronic diseases. Dynamic imaging methods are needed to follow the fate of cargo proteins and their interactions with resident enzymes and folding assistants. Here we applied the Halotag labelling system to study the behavior of proteins with different fates and roles in ESC: a chaperone, an ERAD substrate and an aggregation-prone molecule. Exploiting the Halo property of binding covalently ligands labelled with different fluorochromes, we developed and performed non-radioactive pulse and chase assays to follow sequential waves of proteins in ESC, discriminating between young and old molecules at the single cell level. In this way, we could monitor secretion and degradation of ER proteins in living cells. We can also follow the biogenesis, growth, accumulation and movements of protein aggregates in the ESC. Our data show that protein deposits within ESC grow by sequential apposition of molecules up to a given size, after which novel seeds are detected. The possibility of using ligands with distinct optical and physical properties offers a novel possibility to dynamically follow the fate of proteins in the ESC.  相似文献   
128.
Glioblastoma multiforme (GBM) is the most common and malignant tumor in the central nervous system. One of the contemporary hypotheses postulates that its pathogenesis is associated with the cancer stem cells (CSCs) which originate from mutations in the normal neural stem cells residing in their specific “niches.” Simultaneously with its aggressive development the tumor suppresses the local immune system by different secreted and/or cell expressed factors. Progesterone-induced blocking factor (PIBF) is an immunomodulatory protein with known role in the regulation of the immune response in the reproductive system. Expression of PIBF has been described in some tumors as one of the factors suppressing the anti-tumor immunity. The aim of the present study was to check for the expression of PIBF from cells isolated from six GBMs. To characterize the cultured cells and to study the PIBF expression confocal microscopy, flow cytometry, ELISA, and real-time PCR were used. The results obtained showed expression of markers typical for cancer CSCs and secretion of interleukin 6 by the GBM-derived cultured cells. The results convincingly prove that PIBF is intracellularly expressed by the cultured cells from the all six GBM samples, and this fact is confirmed by three different methods—flow cytometry, confocal microscopy, and real-time PCR. This paper reports for the first time the expression of PIBF by GBM-derived cells cultured in vitro and reveals a new aspect of the immunosuppressive mechanism used by GBM in escaping the immune control.  相似文献   
129.
Hepatitis C virus (HCV) infection is still a serious global health burden. Despite improved therapeutic options, a preventative vaccine would be desirable especially in undeveloped countries. Traditionally, highly conserved epitopes are targets for antibody-based prophylactic vaccines. In HCV-infected patients, however, neutralizing antibodies are primarily directed against hypervariable region I (HVRI) in the envelope protein E2. HVRI is the most variable region of HCV, and this heterogeneity contributes to viral persistence and has thus far prevented the development of an effective HVRI-based vaccine. The primary goal of an antibody-based HCV vaccine should therefore be the induction of cross-reactive HVRI antibodies. In this study we approached this problem by presenting selected cross-reactive HVRI variants in a highly symmetric repeated array on capsid-like particles (CLPs). SplitCore CLPs, a novel particulate antigen presentation system derived from the HBV core protein, were used to deliberately manipulate the orientation of HVRI and therefore enable the presentation of conserved parts of HVRI. These HVRI-CLPs induced high titers of cross-reactive antibodies, including neutralizing antibodies. The combination of only four HVRI CLPs was sufficient to induce antibodies cross-reactive with 81 of 326 (24.8%) naturally occurring HVRI peptides. Most importantly, HVRI CLPs with AS03 as an adjuvant induced antibodies with a 10-fold increase in neutralizing capability. These antibodies were able to neutralize infectious HCVcc isolates and 4 of 19 (21%) patient-derived HCVpp isolates. Taken together, these results demonstrate that the induction of at least partially cross-neutralizing antibodies is possible. This approach might be useful for the development of a prophylactic HCV vaccine and should also be adaptable to other highly variable viruses.  相似文献   
130.
Ghrelin is a 28-amino acid peptide that has significant effects on appetite and growth in humans and animals. The aim of this study was to examine 4th instar larvae of the pest insect Lymantria dispar L. after ghrelin treatment. Parameters included changes in nutritional indices (efficiency of conversion of ingested food, efficiency of conversion of digested food, approximate digestibility); midgut and fat body mass; total proteases, trypsin and leucine aminopeptidase activities in the midgut; number, height and width of columnar and goblet cells and their nuclei in the midgut epithelium and detection of ghrelin-like immunoreactivity in the midgut tissue. Four subpicomolar injections of ghrelin (0.3pmol) or physiological saline (control) were applied every 24h. The nutritional indices were higher in the ghrelin treated than in the control group. Ghrelin treatment was also associated with elevation of midgut mass, induced digestive enzyme activities, increased fat body mass and morphometric changes in columnar and goblet cells. This is the first report of the presence of ghrelin-like hormone in endocrine cells of an insect midgut. Such information provides additional evidence for application of this relatively simple model system in the future studies of the mechanisms underlying of digestion and energy balance in more complex organisms.  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