全文获取类型
收费全文 | 3035篇 |
免费 | 289篇 |
国内免费 | 2篇 |
专业分类
3326篇 |
出版年
2024年 | 2篇 |
2023年 | 23篇 |
2022年 | 79篇 |
2021年 | 125篇 |
2020年 | 82篇 |
2019年 | 94篇 |
2018年 | 97篇 |
2017年 | 86篇 |
2016年 | 140篇 |
2015年 | 216篇 |
2014年 | 233篇 |
2013年 | 278篇 |
2012年 | 302篇 |
2011年 | 251篇 |
2010年 | 178篇 |
2009年 | 115篇 |
2008年 | 215篇 |
2007年 | 176篇 |
2006年 | 161篇 |
2005年 | 140篇 |
2004年 | 104篇 |
2003年 | 88篇 |
2002年 | 72篇 |
2001年 | 14篇 |
2000年 | 9篇 |
1999年 | 11篇 |
1998年 | 14篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 5篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1984年 | 2篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 2篇 |
排序方式: 共有3326条查询结果,搜索用时 0 毫秒
81.
82.
A combination of gene expression ranking and co‐expression network analysis increases discovery rate in large‐scale mutant screens for novel Arabidopsis thaliana abiotic stress genes 下载免费PDF全文
83.
α‐ l‐iduronidase gene‐based therapy using the phiC31 system to treat mucopolysaccharidose type I mice 下载免费PDF全文
Roberta Sessa Stilhano Priscila Keiko Matsumoto Martin Suely Maymone de Melo Vivian Yochiko Samoto Giovani Bravin Peres Yara Maria Correa da Silva Michelacci Flavia Helena da Silva Vanessa Gonçalves Pereira Vania D'Almeida Adriana Taveira da Cruz Miriam Galvonas Jasiulionis Sang Won Han 《The journal of gene medicine》2015,17(1-2):1-13
84.
Ferro FE de Sousa Lima VB Soares NR de Sousa Almondes KG Pires LV Cozzolino SM do Nascimento Marreiro D 《Biological trace element research》2011,143(2):787-793
Alterations in antioxidant defense in obese people with metabolic syndrome can contribute to oxidative stress. This study
assessed the relationship between the parameters of metabolic syndrome and the zincemia, activity of superoxide dismutase,
and glutathione peroxidase enzymes in obese women. Seventy-three premenopausal women, aged between 20 and 50 years, were divided
into two groups: case group, composed of obese (n = 37), and control group, composed of no obese (n = 36). Analyses of zinc intake, parameters of metabolic syndrome, plasma, and erythrocyte zinc, and activities of superoxide
dismutase and glutathione peroxidase were carried out. The mean values of body mass index of obese women and control group
were 34.5 ± 3.4 and 21.7 ± 1.9 kg/m2, respectively (p < 0.05). In the study, body mass index, waist circumference, and zinc intake were higher in obese women than control group
(p < 0.05). The plasma zinc and activity of superoxide dismutase did not show significant differences between obese and controls
(p > 0.05). The values of erythrocyte zinc was 36.4 ± 15.0 μg/gHb and 45.4 ± 14.3 μg/gHb and of glutathione peroxidase was 46.4 ± 19.4 U/gHb
and 36.7 ± 13.6 U/gHb in obese women and controls, respectively (p < 0.05). The study shows that there are alterations in biochemical parameters of zinc in obese women, with low zinc concentrations
in erythrocytes. Regression analysis demonstrates that the erythrocyte zinc and activity of superoxide dismutase enzyme is
influenced by components of the metabolic syndrome, and the plasmatic glucose, body mass index, and waist circumference have
a negative correlation with this enzyme. 相似文献
85.
Fear VS Burchell JT Lai SP Wikstrom ME Blank F von Garnier C Turner DJ Sly PD Holt PG Strickland DS Stumbles PA 《Journal of immunology (Baltimore, Md. : 1950)》2011,187(9):4561-4570
Chronic innocuous aeroallergen exposure attenuates CD4(+) T cell-mediated airways hyperresponsiveness in mice; however, the mechanism(s) remain unclear. We examined the role of airway mucosal dendritic cell (AMDC) subsets in this process using a multi-OVA aerosol-induced tolerance model in sensitized BALB/c mice. Aeroallergen capture by both CD11b(lo) and CD11b(hi) AMDC and the delivery of OVA to airway draining lymph nodes by CD8α(-) migratory dendritic cells (DC) were decreased in vivo (but not in vitro) when compared with sensitized but nontolerant mice. This was functionally significant, because in vivo proliferation of OVA-specific CD4(+) T cells was suppressed in airway draining lymph nodes of tolerized mice and could be restored by intranasal transfer of OVA-pulsed and activated exogenous DC, indicating a deficiency in Ag presentation by endogenous DC arriving from the airway mucosa. Bone marrow-derived DC Ag-presenting function was suppressed in multi-OVA tolerized mice, and allergen availability to airway APC populations was limited after multi-OVA exposure, as indicated by reduced OVA and dextran uptake by airway interstitial macrophages, with diffusion rather than localization of OVA across the airway mucosal surface. These data indicate that inhalation tolerance limits aeroallergen capture by AMDC subsets through a mechanism of bone marrow suppression of DC precursor function coupled with reduced Ag availability in vivo at the airway mucosa, resulting in limited Ag delivery to lymph nodes and hypoproliferation of allergen-specific CD4(+) T cells. 相似文献
86.
Magdalena Sarah Volz Vanessa Suarez-Contreras Mariana E. Mendonca Fernando Santos Pinheiro Lotfi B. Merabet Felipe Fregni 《PloS one》2013,8(1)
Background/Objective
Transcutaneous electrical stimulation has been proven to modulate nervous system activity, leading to changes in pain perception, via the peripheral sensory system, in a bottom up approach. We tested whether different sensory behavioral tasks induce significant effects in pain processing and whether these changes correlate with cortical plasticity.Methodology/Principal Findings
This randomized parallel designed experiment included forty healthy right-handed males. Three different somatosensory tasks, including learning tasks with and without visual feedback and simple somatosensory input, were tested on pressure pain threshold and motor cortex excitability using transcranial magnetic stimulation (TMS). Sensory tasks induced hand-specific pain modulation effects. They increased pain thresholds of the left hand (which was the target to the sensory tasks) and decreased them in the right hand. TMS showed that somatosensory input decreased cortical excitability, as indexed by reduced MEP amplitudes and increased SICI. Although somatosensory tasks similarly altered pain thresholds and cortical excitability, there was no significant correlation between these variables and only the visual feedback task showed significant somatosensory learning.Conclusions/Significance
Lack of correlation between cortical excitability and pain thresholds and lack of differential effects across tasks, but significant changes in pain thresholds suggest that analgesic effects of somatosensory tasks are not primarily associated with motor cortical neural mechanisms, thus, suggesting that subcortical neural circuits and/or spinal cord are involved with the observed effects. Identifying the neural mechanisms of somatosensory stimulation on pain may open novel possibilities for combining different targeted therapies for pain control. 相似文献87.
Xavier Fioramonti Adam Deak Srinidhi Deshpande Lionel Carneiro Chunxue Zhou Nazish Sayed Branly Orban Joshua R. Berlin Luc Pénicaud Corinne Leloup Annie Beuve Vanessa H. Routh 《PloS one》2013,8(7)
Aims
Hypoglycemia is a severe side effect of intensive insulin therapy. Recurrent hypoglycemia (RH) impairs the counter-regulatory response (CRR) which restores euglycemia. During hypoglycemia, ventromedial hypothalamus (VMH) production of nitric oxide (NO) and activation of its receptor soluble guanylyl cyclase (sGC) are critical for the CRR. Hypoglycemia also increases brain reactive oxygen species (ROS) production. NO production in the presence of ROS causes protein S-nitrosylation. S-nitrosylation of sGC impairs its function and induces desensitization to NO. We hypothesized that during hypoglycemia, the interaction between NO and ROS increases VMH sGC S-nitrosylation levels and impairs the CRR to subsequent episodes of hypoglycemia. VMH ROS production and S-nitrosylation were quantified following three consecutive daily episodes of insulin-hypoglycemia (RH model). The CRR was evaluated in rats in response to acute insulin-induced hypoglycemia or via hypoglycemic-hyperinsulinemic clamps. Pretreatment with the anti-oxidant N-acetyl-cysteine (NAC) was used to prevent increased VMH S-nitrosylation.Results
Acute insulin-hypoglycemia increased VMH ROS levels by 49±6.3%. RH increased VMH sGC S-nitrosylation. Increasing VMH S-nitrosylation with intracerebroventricular injection of the nitrosylating agent S-nitroso-L-cysteine (CSNO) was associated with decreased glucagon secretion during hypoglycemic clamp. Finally, in RH rats pre-treated with NAC (0.5% in drinking water for 9 days) hypoglycemia-induced VMH ROS production was prevented and glucagon and epinephrine production was not blunted in response to subsequent insulin-hypoglycemia.Conclusion
These data suggest that NAC may be clinically useful in preventing impaired CRR in patients undergoing intensive-insulin therapy. 相似文献88.
Septate junctions (SJs), similar to tight junctions, function as transepithelial permeability barriers. Gliotactin (Gli) is a cholinesterase-like molecule that is necessary for blood-nerve barrier integrity, and may, therefore, contribute to SJ development or function. To address this hypothesis, we analyzed Gli expression and the Gli mutant phenotype in Drosophila epithelia. In Gli mutants, localization of SJ markers neurexin-IV, discs large, and coracle are disrupted. Furthermore, SJ barrier function is lost as determined by dye permeability assays. These data suggest that Gli is necessary for SJ formation. Surprisingly, Gli distribution only colocalizes with other SJ markers at tricellular junctions, suggesting that Gli has a unique function in SJ development. Ultrastructural analysis of Gli mutants supports this notion. In contrast to other SJ mutants in which septa are missing, septa are present in Gli mutants, but the junction has an immature morphology. We propose a model, whereby Gli acts at tricellular junctions to bind, anchor, or compact SJ strands apically during SJ development. 相似文献
89.
Isabelle Vanessa Mohrenz Patrick Antonietti Stefan Pusch David Capper Jörg Balss Sophia Voigt Susanne Weissert Alicia Mukrowsky Jan Frank Christian Senft Volker Seifert Andreas von Deimling Donat Kögel 《Apoptosis : an international journal on programmed cell death》2013,18(11):1416-1425
Isocitrate dehydrogenase 1 (IDH1) decarboxylates isocitrate to α-ketoglutarate (α-KG) leading to generation of NADPH, which is required to regenerate reduced glutathione (GSH), the major cellular ROS scavenger. Mutation of R132 of IDH1 abrogates generation of α-KG and leads to conversion of α-KG to 2-hydroxyglutarate. We hypothesized that glioma cells expressing mutant IDH1 have a diminished antioxidative capacity and therefore may encounter an ensuing loss of cytoprotection under conditions of oxidative stress. Our study was performed with LN229 cells stably overexpressing IDH1 R132H and wild type IDH1 or with a lentiviral IDH1 knockdown. Quantification of GSH under basal conditions and following treatment with the glutathione reductase inhibitor BCNU revealed significantly lower GSH levels in IDH1 R132H expressing cells and IDH1 KD cells compared to their respective controls. FACS analysis of cell death and ROS production also demonstrated an increased sensitivity of IDH1-R132H-expressing cells and IDH1 KD cells to BCNU, but not to temozolomide. The sensitivity of IDH1-R132H-expressing cells and IDH1 KD cells to ROS induction and cell death was further enhanced with the transaminase inhibitor aminooxyacetic acid and under glutamine free conditions, indicating that these cells were more addicted to glutaminolysis. Increased sensitivity to BCNU-induced ROS production and cell death was confirmed in HEK293 cells inducibly expressing the IDH1 mutants R132H, R132C and R132L. Based on these findings we propose that in addition to its established pro-tumorigenic effects, mutant IDH1 may also limit the resistance of gliomas to specific death stimuli, therefore opening new perspectives for therapy. 相似文献
90.
Victoria J. Bennett Vanessa S. Quinn Patrick A. Zollner 《Biodiversity and Conservation》2013,22(8):1783-1798
Site and wildlife managers globally are under increasing pressure to implement management strategies that address the negative implications of outdoor recreational activities on wildlife. For many rare and isolated species any anthropogenic activities that cause disturbance could potentially be detrimental to existing populations. Understanding how non-consumptive recreation can influence a species may therefore be critical to its preservation. We developed a novel approach to specifically address this need. Using a combination of field surveys and simulation modelling exercises, we (1) explored the responses of endangered Karner blue butterflies (Lycaeides melissa samuelis) to recreation, (2) assessed whether such responses influenced oviposition rate and/or host plant choice and (3) tested alternative management strategies that could alleviate the negative impacts of recreation. Our field surveys confirmed that Karner blues were sensitive to recreational disturbance. Butterflies flushed at similar speeds and distances from recreationists (2.2 m at 0.17 m/s), as they would from natural threats, such as predators (2.2 m at 0.19 m/s). Incorporating female response parameters into a simulation model revealed that regular disturbance could reduce egg laying potential and significantly restrict host plant choice, which in turn, could impact the butterfly’s population dynamics. However, we established that it was possible to effectively offset the implications of recreational disturbance using our simulation modelling approach. For example, extending Karner blue breeding habitat from trails and other public rights of way has the potential to alleviate such disturbance. Our study demonstrates that the potential impact of recreation on species of conservation concern should not be overlooked. 相似文献