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   812篇
  免费   73篇
  国内免费   4篇
  2022年   2篇
  2021年   10篇
  2020年   3篇
  2019年   13篇
  2018年   11篇
  2017年   13篇
  2016年   17篇
  2015年   32篇
  2014年   43篇
  2013年   45篇
  2012年   56篇
  2011年   54篇
  2010年   29篇
  2009年   36篇
  2008年   39篇
  2007年   38篇
  2006年   44篇
  2005年   50篇
  2004年   46篇
  2003年   59篇
  2002年   49篇
  2001年   19篇
  2000年   16篇
  1999年   13篇
  1998年   9篇
  1997年   7篇
  1996年   10篇
  1995年   9篇
  1994年   9篇
  1993年   7篇
  1992年   13篇
  1991年   3篇
  1990年   3篇
  1989年   5篇
  1988年   8篇
  1987年   6篇
  1986年   5篇
  1985年   4篇
  1984年   5篇
  1983年   7篇
  1982年   8篇
  1981年   2篇
  1980年   8篇
  1979年   5篇
  1978年   5篇
  1977年   5篇
  1969年   2篇
  1967年   1篇
  1966年   2篇
  1950年   1篇
排序方式: 共有889条查询结果,搜索用时 15 毫秒
91.

Background

Tobacco smoking is a major contributor to the public health burden and healthcare costs worldwide, but the determinants of smoking behaviours are poorly understood. We conducted a large individual-participant meta-analysis to examine the extent to which work-related stress, operationalised as job strain, is associated with tobacco smoking in working adults.

Methodology and Principal Findings

We analysed cross-sectional data from 15 European studies comprising 166 130 participants. Longitudinal data from six studies were used. Job strain and smoking were self-reported. Smoking was harmonised into three categories never, ex- and current. We modelled the cross-sectional associations using logistic regression and the results pooled in random effects meta-analyses. Mixed effects logistic regression was used to examine longitudinal associations. Of the 166 130 participants, 17% reported job strain, 42% were never smokers, 33% ex-smokers and 25% current smokers. In the analyses of the cross-sectional data, current smokers had higher odds of job strain than never-smokers (age, sex and socioeconomic position-adjusted odds ratio: 1.11, 95% confidence interval: 1.03, 1.18). Current smokers with job strain smoked, on average, three cigarettes per week more than current smokers without job strain. In the analyses of longitudinal data (1 to 9 years of follow-up), there was no clear evidence for longitudinal associations between job strain and taking up or quitting smoking.

Conclusions

Our findings show that smokers are slightly more likely than non-smokers to report work-related stress. In addition, smokers who reported work stress smoked, on average, slightly more cigarettes than stress-free smokers.  相似文献   
92.
Aim To develop and test a simple climate‐based ecophysiological model of above‐ground biomass – an approach that can be applied directly to predicting the effects of climate change on forest carbon stores. Location Humid lowland forests world‐wide. Methods We developed a new approach to modelling the aboveground biomass of old‐growth forest (AGBmax) based on the influences of temperature on gross primary productivity (GPP) and what we call total maintenance cost (TMC), which includes autotrophic respiration as well as leaf, stem and other plant construction required to maintain biomass. We parameterized the models with measured carbon fluxes and tested them by comparing predicted AGBmax with measured AGB for another 109 old‐growth sites. Results Our models explained 57% of the variation in GPP across 95 sites and 79% of the variation in TMC across 17 sites. According to the best‐fit models, the ratio of GPP to maintenance cost per unit biomass (MCB) peaks at 16.5 °C, indicating that this is the air temperature leading to the highest possible AGBmax when temperatures are constant. Seasonal temperature variation generally reduces predicted AGBmax, and thus maritime temperate climates are predicted to have the highest AGBmax. The shift in temperatures from temperate maritime to tropical climates increases MCB more than GPP, and thus decreases AGBmax. Overall, our model explains exactly 50% of the variation in AGB among humid lowland old‐growth forests. Main conclusions Temperature plays an important role in explaining global variation in biomass among humid lowland old‐growth forests, a role that can be understood in terms of the dual effects of temperature on GPP and TMC. Our simple model captures these influences, and could be an important tool for predicting the effects of climate change on forest carbon stores.  相似文献   
93.
The pathogenesis of aortic valve stenosis (AS) is characterized by the accumulation of LDL-derived cholesterol in the diseased valves. Since LDL particles also contain plant sterols, we investigated whether plant sterols accumulate in aortic valve lesions. Serum samples were collected from 82 patients with severe AS and from 12 control subjects. Aortic valves were obtained from a subpopulation of 21 AS patients undergoing valve surgery and from 10 controls. Serum and valvular total cholesterol and noncholesterol sterols were measured by gas-liquid chromatography. Noncholesterol sterols, including both cholesterol precursors and sterols reflecting cholesterol absorption, were detected in serum samples and aortic valves. The higher the ratios to cholesterol of the cholesterol precursors and absorption markers in serum, the higher their ratios in the stenotic aortic valves (r=0.74, P<0.001 for lathosterol and r=0.88, P<0.001 for campesterol). The valvular ratio to cholesterol of lathosterol correlated negatively with the aortic valve area (r= -0.47, P=0.045), suggesting attenuation of cholesterol synthesis with increasing severity of AS. The higher the absorption of cholesterol, the higher the plant sterol contents in stenotic aortic valves. These findings suggest that local accumulation of plant sterols and cholesterol precursors may participate in the pathobiology of aortic valve disease.  相似文献   
94.

Background

No previous studies on the effect of genetic factors on the liability to disability retirement have been carried out. The main aim of this study was to investigate the contribution of genetic factors on disability retirement due to the most common medical causes, including depressive disorders.

Methods

The study sample consisted of 24 043 participants (49.7% women) consisting of 11 186 complete same-sex twin pairs including 3519 monozygotic (MZ) and 7667dizygotic (DZ) pairs. Information on retirement events during 1.1.1975–31.12.2004, including disability pensions (DPs) with diagnoses, was obtained from the Finnish nationwide official pension registers. Correlations in liability for MZ and DZ twins and discrete time correlated frailty model were used to investigate the genetic liability to age at disability retirement.

Results

The 30 year cumulative incidence of disability retirement was 20%. Under the best fitting genetic models, the heritability estimate for DPs due to any medical cause was 0.36 (95% CI 0.32–0.40), due to musculoskeletal disorders 0.37 (0.30–0.43), cardiovascular diseases 0.48 (0.39–0.57), mental disorders 0.42 (0.35–0.49) and all other reasons 0.24 (0.17–0.31). The effect of genetic factors decreased with increasing age of retirement. For DP due to depressive disorders, 28% of the variance was explained by environmental factors shared by family members (95% CI 21–36) and 58% of the variance by the age interval specific environmental factors (95% CI 44–71).

Conclusions

A moderate genetic contribution to the variation of disability retirement due to any medical cause was found. The genetic effects appeared to be stronger at younger ages of disability retirement suggesting the increasing influence of environmental factors not shared with family members with increasing age. Familial aggregation in DPs due to depressive disorders was best explained by the common environmental factors and genetic factors were not needed to account for the pattern of familial aggregation.  相似文献   
95.
We found that d-mannose dose-dependently decreases hyaluronan synthesis in cultured epidermal keratinocytes to approximately 50%, whereas glucose, galactose, and fructose up to 20 mm concentration had no effect. The full inhibition occurred within 3 h following introduction of mannose and did not involve down-regulation of hyaluronan synthase (Has1-3) mRNA. Following introduction of mannose, there was an approximately 50% reduction in the cellular concentration of UDP-N-acetylhexosamines (UDP-HexNAc, i.e. UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine). On the other hand, 2 mm glucosamine in the culture medium increased UDP-HexNAc content, stimulated hyaluronan secretion, and negated the effect of mannose, supporting the notion that the inhibition by mannose on hyaluronan synthesis was because of down-regulated UDP-HexNAc content. The content of UDP-glucuronic acid, the other building block for hyaluronan synthesis, was not reduced by mannose but declined from 39 to 14% of controls by 0.2-1.0 mm 4-methylumbelliferone, another compound that inhibits hyaluronan synthesis. Applying 4-methylumbelliferone and mannose together produced the expected reductions in both UDP sugars but no additive reduction in hyaluronan production, indicating that the concentration of each substrate alone can limit hyaluronan synthesis. Mannose is a potentially useful tool in studies on hyaluronan-dependent cell functions, as demonstrated by reduced rates of keratinocyte proliferation and migration, functions known to depend on hyaluronan synthesis.  相似文献   
96.
An HPLC method with evaporative light-scattering detection (ELSD) was optimized and validated for the simultaneous quantitation of cholesteryl esters (CEs), triacylglycerols (TGs), free cholesterol (FC) and phosphatidylcholine (PC) in human plasma. The separation of CEs from TGs, the most variable plasma lipid class, was improved by speeding up the gradient steps and by increasing the re-equilibration time between runs. The calibrations were made at levels of 0.14–14 μg lipid/injection. The intra- and inter-day precision values of the method ranged between 1.9 and 4.5 and 2.3–7.2% (RSD, n=6), respectively, including determinations at two concentration levels. In comparison to other lipid classes, quantitation of PC proved to be equally repeatable despite its lowest detector response. The relative recoveries varied from 97.0 to 110.3%, showing good accuracy of the method. The methodological variation of the lipid classes covered 0.6–3.1% of their total variation in the study population (n=48). The CE/FC ratio showed an even closer relationship with phospholipid linoleic acid (18:2n−6; r=0.65, P<0.001) than with serum cholesterol levels, while eicosapentaenoic acid (20:5n−3) was significantly associated with PC (r=0.41, P<0.01). The CE/FC ratio increased (P<0.01) during soyabean oil substitution and the level of PC increased (P<0.01) during cold-pressed rapeseed oil substitution.  相似文献   
97.
Because nest predation is the major source of nesting mortality in birds, site-specific predation risk may play an important role in determining birds' ability to select nest sites that reduce predation risk. This possibility has not been adequately tested. Here we report on 5-year experiments by which we studied, independently from birds' earlier experience with specific nest boxes, both the selection and predation risk of nest sites in the common goldeneye (Bucephala clangula). New, previously unoccupied nest boxes were erected in two habitat types on three study areas. Experimentally measured predation risk in the nest boxes varied between 0 and 1.0, i.e. goldeneye females could select a nest site along a wide gradient of possible predation-risk values. We did not find a difference in predation risk between occupied and unoccupied nest boxes, nor was the order of nest box occupation associated with predation risk. A power analysis revealed that our test had reasonably high power to reject a false null hypothesis. Our results suggest that common goldeneye females likely have not evolved an ability to assess predation risk of new, previously unoccupied nest sites.  相似文献   
98.
A continuous rat epidermal cell line (rat epidermal keratinocyte; REK) formed a morphologically well-organized epidermis in the absence of feeder cells when grown for 3 weeks on a collagen gel in culture inserts at an air-liquid interface, and developed a permeability barrier resembling that of human skin. By 2 weeks, an orthokeratinized epidermis evolved with the suprabasal layers exhibiting the differentiation markers keratin 10, involucrin, and filaggrin. Granular cells with keratohyalin granules and lamellar bodies, and corneocytes with cornified envelopes and tightly packed keratin filaments were present. Morphologically, vitamin C supplementation of the culture further enhanced the normal wavy pattern of the stratum corneum, the number of keratohyalin granules present, and the quantity and organization of intercellular lipid lamellae in the interstices of the stratum corneum. The morphological enhancements observed with vitamin C correlated with improved epidermal barrier function, as indicated by reduction of the permeation rates of tritiated corticosterone and mannitol, and transepidermal water loss, with values close to those of human skin. Moreover, filaggrin mRNA was increased by vitamin C, and western blots confirmed higher levels of profilaggrin and filaggrin, suggesting that vitamin C also influences keratinocyte differentiation in aspects other than the synthesis and organization of barrier lipids. The unique REK cell line in organotypic culture thus provides an easily maintained and reproducible model for studies on epidermal differentiation and transepidermal permeation.  相似文献   
99.
The elimination from the blood of 51Cr-labelled mouse erythrocytes modified with trinitrophenyl (TNP) groups was followed in mice. After 24 hours, when a stable concentration of the labelled erythrocytes has been attained, monoclonal anti-TNP-antibodies were given intravenously, either in free, soluble form, or bound to microparticles containing immobilized protein A. The anti-TNP-antibodies induced a rapid elimination of the TNP- and 51Cr-labelled erythrocytes. Over the 8-hours time period studied, the elimination rate was significantly faster when the antibodies were administered bound to the particles. After the elimination of the target cells, the radioactivity was found in the liver, spleen and bone marrow. These results and relevant control experiments indicate that a solid carrier 1. can be directed to a specific target cell with a specific antibody and 2. can induce a rapid elimination of the target cell from the circulation.  相似文献   
100.

Background  

We have previously set up an in vitro mesenchymal-epithelial cell co-culture model which mimics the intestinal crypt villus axis biology in terms of epithelial cell differentiation. In this model the fibroblast-induced epithelial cell differentiation from secretory crypt cells to absorptive enterocytes is mediated via transforming growth factor-β (TGF-β), the major inhibitory regulator of epithelial cell proliferation known to induce differentiation in intestinal epithelial cells. The aim of this study was to identify novel genes whose products would play a role in this TGF-β-induced differentiation.  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