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   691篇
  免费   47篇
  国内免费   32篇
  770篇
  2022年   19篇
  2021年   19篇
  2020年   11篇
  2019年   14篇
  2018年   24篇
  2017年   11篇
  2016年   25篇
  2015年   30篇
  2014年   26篇
  2013年   47篇
  2012年   40篇
  2011年   58篇
  2010年   38篇
  2009年   28篇
  2008年   25篇
  2007年   31篇
  2006年   42篇
  2005年   28篇
  2004年   16篇
  2003年   17篇
  2002年   18篇
  2001年   13篇
  2000年   11篇
  1999年   7篇
  1998年   14篇
  1997年   11篇
  1996年   7篇
  1995年   4篇
  1994年   8篇
  1992年   9篇
  1990年   3篇
  1989年   6篇
  1988年   4篇
  1987年   6篇
  1985年   3篇
  1984年   6篇
  1983年   5篇
  1982年   5篇
  1981年   10篇
  1980年   8篇
  1978年   3篇
  1977年   5篇
  1973年   7篇
  1971年   3篇
  1958年   3篇
  1957年   2篇
  1955年   4篇
  1954年   2篇
  1949年   5篇
  1948年   2篇
排序方式: 共有770条查询结果,搜索用时 0 毫秒
91.
We studied the mechanisms underlying support of body load in posture and walking in serially homologous legs of cockroaches. Activities of the trochanteral extensor muscle in the front or middle legs were recorded neurographically while animals were videotaped. Body load was increased via magnets attached to the thorax and varied through a coil below the substrate. In posture, tonic firing of the slow trochanteral extensor motoneuron (Ds) in each leg was strongly modulated by changing body load. Rapid load increases produced decreases in body height and sharp increments in extensor firing. The peak of extensor activity more closely approximated the maximum velocity of body displacement than the body position. In walking, extensor bursts in front and middle legs were initiated during swing and continued into the stance phase. Moderate tonic increases in body load elicited similar, specific, phase dependent changes in both legs: extensor firing was not altered in swing but was higher after foot placement in stance. These motor adjustments to load are not anticipatory but apparently depend upon sensory feedback. These data are consistent with previous findings in the hind legs and support the idea that body load is countered by common motor mechanisms in serially homologous legs.  相似文献   
92.
Burkholderia cenocepacia is an opportunistic pathogen that causes chronic infection and induces progressive respiratory inflammation in cystic fibrosis patients. Recognition of bacteria by mononuclear cells generally results in the activation of caspase-1 and processing of IL-1β, a major proinflammatory cytokine. In this study, we report that human pyrin is required to detect intracellular B. cenocepacia leading to IL-1β processing and release. This inflammatory response involves the host adapter molecule ASC and the bacterial type VI secretion system (T6SS). Human monocytes and THP-1 cells stably expressing either small interfering RNA against pyrin or YFP-pyrin and ASC (YFP-ASC) were infected with B. cenocepacia and analyzed for inflammasome activation. B. cenocepacia efficiently activates the inflammasome and IL-1β release in monocytes and THP-1. Suppression of pyrin levels in monocytes and THP-1 cells reduced caspase-1 activation and IL-1β release in response to B. cenocepacia challenge. In contrast, overexpression of pyrin or ASC induced a robust IL-1β response to B. cenocepacia, which correlated with enhanced host cell death. Inflammasome activation was significantly reduced in cells infected with T6SS-defective mutants of B. cenocepacia, suggesting that the inflammatory reaction is likely induced by an as yet uncharacterized effector(s) of the T6SS. Together, we show for the first time, to our knowledge, that in human mononuclear cells infected with B. cenocepacia, pyrin associates with caspase-1 and ASC forming an inflammasome that upregulates mononuclear cell IL-1β processing and release.  相似文献   
93.
Giardia lamblia, the causative agent of giardiasis, is an intestinal infection with worldwide distribution and high rates of prevalence. Increased resistance of the parasite and the side effects of the reference drugs employed in the treatment of giardiasis make it necessary to seek new therapeutic agents. Therefore,the aim of this study was to examine the activity of hexadecylphosphocholine (miltefosine), a membrane active alkylphospholipid, that is licensed as an antileishmanial agent against giardiasis. The efficacy of miltefosine was evaluated both in vitro and in vivo in Swiss albino mice. Results of the in vitro testing revealed susceptibility of G. lamblia trophozoites to miltefosine with the following effective concentrations:EC50s of between 20 and 40 lM, and EC90s of between 20 and 80 lM. Immediate total lysis of the organisms was achieved by 100 lM. In vivo testing showed that oral administration of miltefosine,in a daily dose regimen course of 20 mg/kg for three successive days, to infected mice resulted in total elimination of the parasite from the intestine and amelioration of intestinal pathology. Scanning and transmission electron microscopy studies revealed that miltefosine induced severe morphological alterations to G. lamblia trophozoites, mainly at the level of cell membrane and adhesive disc. In conclusion,we believe that this is the first study highlighting G. lamblia as a possible new target for miltefosine.  相似文献   
94.
Scientists predict that global agricultural lands will expand over the next few decades due to increasing demands for food production and an exponential increase in crop‐based biofuel production. These changes in land use will greatly impact biogeochemical and biogeophysical cycles across the globe. It is therefore important to develop models that can accurately simulate the interactions between the atmosphere and important crops. In this study, we develop and validate a new process‐based sugarcane model (included as a module within the Agro‐IBIS dynamic agro‐ecosystem model) which can be applied at multiple spatial scales. At site level, the model systematically under/overestimated the daily sensible/latent heat flux (by ?10.5% and 14.8%, H and λE, respectively) when compared against the micrometeorological observations from southeast Brazil. The model underestimated ET (relative bias between ?10.1% and –12.5%) when compared against an agro‐meteorological field experiment from northeast Australia. At the regional level, the model accurately simulated average yield for the four largest mesoregions (clusters of municipalities) in the state of São Paulo, Brazil, over a period of 16 years, with a yield relative bias of ?0.68% to 1.08%. Finally, the simulated annual average sugarcane yield over 31 years for the state of Louisiana (US) had a low relative bias (?2.67%), but exhibited a lower interannual variability than the observed yields.  相似文献   
95.
More robust cattle have the potential to increase farm profitability, improve animal welfare, reduce the contribution of ruminant livestock to greenhouse gas emissions and decrease the risk of food shortages in the face of increased variability in the farm environment. Breeding is a powerful tool for changing the robustness of cattle; however, insufficient recording of breeding goal traits and selection of animals at younger ages tend to favour genetic change in productivity traits relative to robustness traits. This paper has extended a previously proposed theory of artificial evolution to demonstrate, using deterministic simulation, how choice of breeding scheme design can be used as a tool to manipulate the direction of genetic progress, whereas the breeding goal remains focussed on the factors motivating individual farm decision makers. Particular focus was placed on the transition from progeny testing or mass selection to genomic selection breeding strategies. Transition to genomic selection from a breeding strategy where candidates are selected before records from progeny being available was shown to be highly likely to favour genetic progress in robustness traits relative to productivity traits. This was shown even with modest numbers of animals available for training and when heritability for robustness traits was only slightly lower than that for productivity traits. When transitioning from progeny testing to a genomic selection strategy without progeny testing, it was shown that there is a significant risk that robustness traits could become less influential in selection relative to productivity traits. Augmentations of training populations using genotyped cows and support for industry-wide improvements in phenotypic recording of robustness traits were put forward as investment opportunities for stakeholders wishing to facilitate the application of science on robust cattle into improved genetic selection schemes.  相似文献   
96.
A new species, Eugenia marambaiensis M.C.Souza & M.P.Morim, is described and illustrated. It is characterized by having large translucent gland dots densely distributed on the leaves, with a caudate apex and slightly wavy margins and a glabrous raceme, with only two flowers. Eugenia marambaiensis was only found in the locality of Restinga da Marambaia, Rio de Janeiro, Brazil. © 2008 The Linnean Society of London, Botanical Journal of the Linnean Society, 2008, 158 , 306–308.  相似文献   
97.
One of the best examples of differentiation and hybridization among South American passerine birds is exhibited by Icterus cayanensis (Epaulet Oriole) and Icterus chrysocephalus (Moriche Oriole). Icterus chrysocephalus is a monotypic species restricted to northern South America. Icterus cayanensis is a polytypc species that ranges from Suriname and French Guyana to northern Argentina. Five subspecies are recognized to I. cayanensis. Hybrid zones are known between I. cayanensis and I. chrysocephalus as well as between subspecies of I. cayanenis, even though character variation has never been adequately assessed and mapped. Although molecular data support the hypothesis that I. cayanensis and I. chrysocephalus form a monophyletic group, they do not support the species limits currently recognized within this group. We analysed the geographic variation of plumage characters along the range of this group to map the geographic variation of individual plumage characters and identify the populations that have uniform phenotypic character expression and therefore represent genuine phylogenetic species. We also used molecular data to investigate the phylogenetic relationships among these species. Geographic variation of plumage characters, habitat preferences and molecular data identified four species within I. cayanensis–chrysocephalus clade: an Amazonian species group, formed by I. cayanensis and I. chrysocephalus and a Southern species group composed of I. pyrrhopterus and I. tibialis. The Amazonian species are separated by a relatively narrow hybrid zone along the Amazon valley, whereas the Southern species are separated by a hybrid zone that is larger than the ranges of the two species individually. © 2008 The Linnean Society of London, Biological Journal of the Linnean Society, 2008, 95 , 583–597.  相似文献   
98.
The horn fly, Haematobia irritans (L.) (Diptera: Muscidae), is a cosmopolitan livestock pest that has caused a great negative impact on the animal production sector throughout the world. Here, we describe 10 polymorphic microsatellite loci isolated from H. irritans. The number of alleles found ranged from two to eight per locus and the expected heterozygosity from 0.1421 to 0.7702. These loci are potentially useful for the fine-scale genetic characterization of horn fly populations and provide fundamental information for pest management and planning of control programs.  相似文献   
99.
Enhancement of gene transfer using YIGSR analog of Tat-derived peptide   总被引:1,自引:0,他引:1  
Cell penetrating peptide based gene carriers are notably known for low level of gene transfer. To remedy this, as laminin receptor (LR) has been previously linked to tumor metastasis, the LR-binding domain (YIGSR) as well as a scrambled sequence (SGIYR) were added to Tat-derived peptide sequence (YIGSR-Tat and SGIYR-Tat respectively). Peptides cellular uptake was assessed with high-LR (HT1080) and low-LR (HT29) cell lines by flow cytometry. Their ability to form complexes with DNA was examined using YOPRO-1 fluorescence assay and their transfection efficiencies evaluated using a luciferase reporter gene assay. DNA complexes were formed at (+/-) charge ratios as low as 2:1. While no conclusion could be drawn on the effect of YIGSR sequence on peptides uptake in both cell lines, a significant improvement in gene transfection in HT1080 cells was achieved using YIGSR-Tat compared to Tat and SGIYR-Tat. Additionally this increased efficiency was inhibited by excess free YIGSR. No significant difference in transfection efficiency was observed between Tat, SGIYR-Tat and YIGSR-Tat based complexes in HT29 cells. These studies demonstrate that attachment of receptor-binding ligand (YIGSR) to Tat-derived peptide can improve the efficiency of gene transfer in LR-positive cells (HT1080).  相似文献   
100.
Many aspects of the pathology in beta-hemoglobinopathies (beta-thalassemia and sickle cell anemia) are mediated by oxidative stress. In the present study we tested a novel thiol compound, N-acetylcysteine amide (AD4), the amide form of N-acetyl cysteine (NAC) for its antioxidant effects. Using flow-cytometry, we showed that in vitro treatment of blood cells from beta-thalassemic patients with AD4 elevated the reduced glutathione (GSH) content of red blood cells (RBC), platelets and polymorphonuclear (PMN) leukocytes, and reduced their ROS. These effects resulted in a significant reduced sensitivity of thalassemic RBC to hemolysis and phagocytosis by macrophages. Intra-peritoneal injection of AD4 to beta-thalassemic mice (150 mg/kg) reduced the parameters of oxidative stress (p<0.001). Our results show the superiority of AD4, compared to NAC, in reducing oxidative stress markers in thalassemic cells both in vitro and in vivo.  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