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   3241篇
  免费   260篇
  国内免费   186篇
  2023年   20篇
  2022年   53篇
  2021年   124篇
  2020年   92篇
  2019年   118篇
  2018年   103篇
  2017年   89篇
  2016年   132篇
  2015年   154篇
  2014年   208篇
  2013年   252篇
  2012年   241篇
  2011年   202篇
  2010年   147篇
  2009年   135篇
  2008年   157篇
  2007年   158篇
  2006年   122篇
  2005年   99篇
  2004年   115篇
  2003年   106篇
  2002年   105篇
  2001年   81篇
  2000年   52篇
  1999年   48篇
  1998年   28篇
  1997年   30篇
  1996年   22篇
  1995年   18篇
  1994年   36篇
  1993年   21篇
  1992年   47篇
  1991年   34篇
  1990年   24篇
  1989年   29篇
  1988年   23篇
  1987年   21篇
  1986年   16篇
  1985年   18篇
  1984年   12篇
  1983年   14篇
  1982年   14篇
  1981年   11篇
  1980年   12篇
  1979年   10篇
  1977年   8篇
  1975年   7篇
  1974年   9篇
  1970年   8篇
  1969年   12篇
排序方式: 共有3687条查询结果,搜索用时 15 毫秒
111.
中医体质学以人为研究对象,为了研究不同体质构成特点、演变规律、影响因素、分类标准,从而指导疾病的预防、诊治、康复与养生。目前关于生理和病理状态下的中医体质研究日益受到关注,因为对其研究符合中医”治未病”的理念,而关于少数民族的中医体质类型研究开展较少,但对少数民族之间和汉族之间中医体质的比较研究及与生活习惯,生活环境的联系将能更好地说明先天因素和后天环境对中医体质形成的影响。本文就这一领域的研究现状进行总结,对少数民族中医体质的研究一方面可为少数民族人群的疾病防治提供依据,另一方面有助于中医体质形成机理的阐明。  相似文献   
112.
113.
As a second messenger, Ca2+ plays a major role in cold induced transduction via stimulus-specific increases in [Ca2+]cyt, which is called calcium signature. During this process, CAXs (Ca2+/H+ exchangers) play critical role. For the first time, a putative Ca2+/H+ exchanger GhCAX3 gene from upland cotton (Gossypium hirsutum cv. ‘YZ-1′) was isolated and characterized. It was highly expressed in all tissues of cotton except roots and fibers. This gene may act as a regulator in cotton’s response to abiotic stresses as it could be up-regulated by Ca2+, NaCl, ABA and cold stress. Similar to other CAXs, it was proved that GhCAX3 also had Ca2+ transport activity and the N-terminal regulatory region (NRR) through yeast complementation assay. Over-expression of GhCAX3 in tobacco showed less sensitivity to ABA during seed germination and seedling stages, and the phenotypic difference between wild type (WT) and transgenic plants was more significant when the NRR was truncated. Furthermore, GhCAX3 conferred cold tolerance in yeast as well as in tobacco seedlings based on physiological and molecular studies. However, transgenic plant seeds showed more sensitivity to cold stress compared to WT during seed germination, especially when expressed in N-terminal truncated version. Finally, the extent of sensitivity in transgenic lines was more severe than that in WT line under sodium tungstate treatment (an ABA repressor), indicating that ABA could alleviate cold sensitivity of GhCAX3 seeds, especially in short of its NRR. Meanwhile, we also found that overexpression of GhCAX3 could enhance some cold and ABA responsive marker genes. Taken together, these results suggested that GhCAX3 plays important roles in the cross-talk of ABA and cold signal transduction, and compared to full-length of GhCAX3, the absence of NRR could enhance the tolerance or sensitivity to cold stress, depending on seedling’s developmental stages.  相似文献   
114.
Stem cell therapy is a promising treatment for incurable disorders including Huntington''s disease (HD). Adipose-derived stem cell (ASC) is an easily available source of stem cells. Since ASCs can be differentiated into nervous stem cells, it has clinically feasible potential for neurodegenerative disease. In addition, ASCs secrete various anti-apoptotic growth factors, which improve the symptoms of disease from transplanted ASCs. Thus, cell-free extracts of ASCs (ASCs-E) could be a potential candidate for treatment of HD. Here, we investigated effects of ASCs-E on R6/2 HD mouse model and neuronal cells. In R6/2 HD model, injection of ASCs-E improved the performance in Rotarod test. ASCs-E also ameliorated striatal atrophy and mutant huntingtin aggregation in the striatum. In Western blot increased expressions of p-Akt, p-CREB and PGC1α were noted by injection of ASCs-E, when comparing to the R6/2 HD model. Neuro2A neuroblastoma cells treated with ASCs-E showed increased expression of p-CREB and PGC1α. In conclusion, ASCs-E delayed disease progression in animal model of HD by restoring of CREB-PGC1α pathway and could be a potential resource for treatment of HD.  相似文献   
115.

Background

11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) activates glucocorticoid locally in liver and fat tissues to aggravate metabolic syndrome. 11β-HSD1 selective inhibitor can be used to treat metabolic syndrome. Curcumin and its derivatives as selective inhibitors of 11β-HSD1 have not been reported.

Methodology

Curcumin and its 12 derivatives were tested for their potencies of inhibitory effects on human and rat 11β-HSD1 with selectivity against 11β-HSD2. 200 mg/kg curcumin was gavaged to adult male Sprague-Dawley rats with high-fat-diet-induced metabolic syndrome for 2 months.

Results and Conclusions

Curcumin exhibited inhibitory potency against human and rat 11β-HSD1 in intact cells with IC50 values of 2.29 and 5.79 µM, respectively, with selectivity against 11β-HSD2 (IC50, 14.56 and 11.92 µM). Curcumin was a competitive inhibitor of human and rat 11β-HSD1. Curcumin reduced serum glucose, cholesterol, triglyceride, low density lipoprotein levels in high-fat-diet-induced obese rats. Four curcumin derivatives had much higher potencies for Inhibition of 11β-HSD1. One of them is (1E,4E)-1,5-bis(thiophen-2-yl) penta-1,4-dien-3-one (compound 6), which had IC50 values of 93 and 184 nM for human and rat 11β-HSD1, respectively. Compound 6 did not inhibit human and rat kidney 11β-HSD2 at 100 µM. In conclusion, curcumin is effective for the treatment of metabolic syndrome and four novel curcumin derivatives had high potencies for inhibition of human 11β-HSD1 with selectivity against 11β-HSD2.  相似文献   
116.

Background

There has been no comprehensive study on biochemical characterization of insecticide resistance mechanisms in field populations of Malaysian Culex quinquefasciatus. To fill this void in the literature, a nationwide investigation was performed to quantify the enzyme activities, thereby attempting to characterize the potential resistance mechanisms in Cx. quinquefasciatus in residential areas in Malaysia.

Methodology/Principal Findings

Culex quinquefasciatus from 14 residential areas across 13 states and one federal territory were subjected to esterases, mixed function oxidases, glutathione-S-transferase and insensitive acetylcholinesterase assays. Enzyme assays revealed that α-esterases and β-esterases were elevated in 13 populations and 12 populations, respectively. Nine populations demonstrated elevated levels of mixed function oxidases and glutathione-S-transferase. Acetylcholinesterase was insensitive to propoxur in all 14 populations. Activity of α-esterases associated with malathion resistance was found in the present study. In addition, an association between the activity of α-esterases and β-esterases was also demonstrated.

Conclusions/Significance

The present study has characterized the potential biochemical mechanisms in contributing towards insecticide resistance in Cx. quinquefasciatus field populations in Malaysia. Identification of mechanisms underlying the insecticide resistance will be beneficial in developing effective mosquito control programs in Malaysia.  相似文献   
117.

Background

The secondary attack rate of hepatitis A virus (HAV) among contacts of cases is up to 50%. Historically, contacts were offered immunoglobulin (IG, a human derived blood product) as post-exposure prophylaxis (PEP). Amid safety concerns about IG, HAV vaccine is increasingly recommended instead. Public health authorities’ recommendations differ, particularly for healthy contacts ≥40 years old, where vaccine efficacy data is limited. We evaluated routine use of HAV vaccine as an alternative to immunoglobulin in PEP, in those considered at low risk of severe infection in the Netherlands.

Methods

Household contacts of acute HAV cases notified in Amsterdam (2004-2012) were invited ≤14 days post-exposure, for baseline anti-HAV testing and PEP according to national guidelines: immunoglobulin if at risk of severe infection, or hepatitis A vaccine if healthy and at low risk (aged <30, or, 30-50 years and vaccinated <8 days post-exposure). Incidence of laboratory confirmed secondary infection in susceptible contacts was assessed 4-8 weeks post-exposure. In a vaccinated subgroup, relative risk (RR) of secondary infection with estimated using Poisson regression.

Results

Of 547 contacts identified, 191 were susceptible to HAV. Per-protocol, 167 (87%) were vaccinated (mean:6.7 days post-exposure, standard deviation(sd)=3.3) and 24 (13%) were given immunoglobulin (mean:9.7 days post-exposure, sd=2.8). At follow-up testing, 8/112 (7%) had a laboratory confirmed infection of whom 7 were symptomatic. All secondary infections occurred in vaccinated contacts, and half were >40 years of age. In healthy contacts vaccinated per-protocol ≤8 days post-exposure, RRref. ≤15 years of secondary infection in those >40 years was 12.0 (95%CI:1.3-106.7).

Conclusions

Timely administration of HAV vaccine in PEP was feasible and the secondary attack rate was low in those <40 years. Internationally, upper age-limits for post-exposure vaccination vary. Pending larger studies, immunoglobulin should be considered PEP of choice in people >40 years of age and those vulnerable to severe disease.  相似文献   
118.
Recent clinical trials raised concerns regarding the cardiovascular toxicity of selective cyclooxygenase-2 (COX-2) inhibitors. Many active dietary factors are reported to suppress carcinogenesis by targeting COX-2. A major question was accordingly raised: why has the lifelong use of phytochemicals that likely inhibit COX-2 presumably not been associated with adverse cardiovascular side effects. To answer this question, we selected a library of dietary-derived phytochemicals and evaluated their potential cardiovascular toxicity in human umbilical vein endothelial cells. Our data indicated that the possibility of cardiovascular toxicity of these dietary phytochemicals was low. Further mechanistic studies revealed that the actions of these phytochemicals were similar to aspirin in that they mainly inhibited COX-1 rather than COX-2, especially at low doses.  相似文献   
119.
Wu  Yuexia  Lian  Keqian  Sun  Cong 《Molecular and cellular biochemistry》2020,463(1-2):161-173
Molecular and Cellular Biochemistry - Alzheimer’s disease (AD) is the leading cause of dementia, which characterized by toxic senile plaques is composed of amyloid-β (Aβ)....  相似文献   
120.
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