全文获取类型
收费全文 | 1419篇 |
免费 | 162篇 |
出版年
2023年 | 5篇 |
2022年 | 5篇 |
2021年 | 20篇 |
2020年 | 22篇 |
2019年 | 16篇 |
2018年 | 21篇 |
2017年 | 30篇 |
2016年 | 58篇 |
2015年 | 77篇 |
2014年 | 86篇 |
2013年 | 91篇 |
2012年 | 123篇 |
2011年 | 119篇 |
2010年 | 77篇 |
2009年 | 58篇 |
2008年 | 105篇 |
2007年 | 90篇 |
2006年 | 81篇 |
2005年 | 81篇 |
2004年 | 91篇 |
2003年 | 75篇 |
2002年 | 62篇 |
2001年 | 17篇 |
2000年 | 13篇 |
1999年 | 15篇 |
1998年 | 19篇 |
1997年 | 17篇 |
1996年 | 9篇 |
1995年 | 9篇 |
1994年 | 13篇 |
1993年 | 11篇 |
1992年 | 2篇 |
1991年 | 6篇 |
1990年 | 4篇 |
1989年 | 8篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1984年 | 5篇 |
1983年 | 9篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1978年 | 1篇 |
1975年 | 1篇 |
1974年 | 3篇 |
1973年 | 1篇 |
1972年 | 2篇 |
1971年 | 1篇 |
1970年 | 2篇 |
1968年 | 2篇 |
排序方式: 共有1581条查询结果,搜索用时 171 毫秒
141.
Roodenburg AJ Schlatmann A Dötsch-Klerk M Daamen R Dong J Guarro M Stergiou M Sayed N Ronoh E Jansen L Seidell JC 《PloS one》2011,6(2):e14721
Introduction
Nutrient profiling is defined as the science of categorising foods based on their nutrient composition. The Choices Programme is a nutrient profile system with criteria that determine whether foods are eligible to carry a “healthier option” stamp. The Daily Menu Method which has been developed to evaluate these criteria is described here. This method simulates the change in calculated nutrient intakes which would be the result of consumers changing their diets in favour of food products that comply with the criteria.Methods
Average intakes of energy, trans fatty acids (TFA), saturated fatty acids (SAFA), sodium, added sugar and fibre were derived from dietary intake studies and food consumption surveys of 7 countries: The Netherlands, Greece, Spain, the USA, Israel, China and South Africa. For each of the key nutrients, these average intakes were translated into three Typical Daily Menus per country. Average intakes based on these three menus were compared with average intakes from three Choices Daily Menus. To compose the Choices Menus, foods from the Typical Menus that did not comply with the Choices criteria were replaced with foods that did comply and are available on the market.Results
Comparison of intakes from the Choices Menus with the survey data showed that calculated intakes of energy, SAFA, TFA, sodium and added sugar were reduced. Fibre intakes were increased. The size of the effect differed per country.Conclusion
The Daily Menu Method is a useful means to predict the potential effects of nutrient profiles such as the Choices criteria, on daily nutrient intakes. The method can be applied internationally and confirms that the criteria of the Choices Programme are in line with the aim of the programme: to improve nutrient intakes in the direction of the recommendations. 相似文献142.
Windholz J Kovacs P Tönjes A Dittrich K Blüher S Kiess W Stumvoll M Körner A 《PloS one》2011,6(7):e22101
Objective
Recent genome-wide association studies identified novel candidate genes for fasting and 2 h blood glucose and insulin levels in adults. We investigated the role of four of these loci (ADCY5, GIPR, GCKR and VPS13C) in early impairment of glucose and insulin metabolism in children.Research Design and Methods
We genotyped four variants (rs2877716; rs1260326; rs10423928; rs17271305) in 638 Caucasian children with detailed metabolic testing including an oGTT and assessed associations with measures of glucose and insulin metabolism (including fasting blood glucose, insulin levels and insulin sensitivity/secretion indices) by linear regression analyses adjusted for age, sex, BMI-SDS and pubertal stage.Results
The major allele (C) of rs2877716 (ADCY5) was nominally associated with decreased fasting plasma insulin (P = 0.008), peak insulin (P = 0.009) and increased QUICKI (P = 0.016) and Matsuda insulin sensitivity index (P = 0.013). rs17271305 (VPS13C) was nominally associated with 2 h blood glucose (P = 0.009), but not with any of the insulin or insulin sensitivity parameters. We found no association of the GIPR and GCKR variants with parameters of glucose and insulin metabolism. None of the variants correlated with anthropometric traits such as height, WHR or BMI-SDS, which excluded potential underlying associations with obesity.Conclusions
Our data on obese children indicate effects of genetic variation within ADCY5 in early impairment of insulin metabolism and VPS13C in early impairment of blood glucose homeostasis. 相似文献143.
The pro-inflammatory cytokines interleukin 1 (IL-1) and 6 (IL-6) are crucially involved in the regulation of a multitude of physiological processes, in particular coordinating the immune response upon bacterial infection and tissue injury. Both interleukins induce complex signalling cascades and trigger the production of mitogenic, pro-proliferative, anti-apoptotic, chemotactic, and pro-angiogenic factors thereby affecting the delicate balance between regeneration vs. invasive growth, tumourigenesis and metastasis. Moreover, several links to insulin resistance have been found within their associated signalling networks. Focusing on this from a systems biology perspective, we introduce comprehensive large-scale network models of IL-1 and IL-6 signalling which are based on a logical modelling approach and reflect the current biological knowledge. Theoretical network analysis enabled us to uncover general topological features and to make testable predictions on the stimulus-response behaviour of the networks. In this context, non-intuitive network-wide species dependencies as well as structures of regulatory feedback and feed-forward mechanisms could be characterised. By integrating high-throughput phosphoproteomic data from primary human hepatocytes we optimised the model structures to obtain models with high prediction accuracy for hepatocytes. Our model-based data analysis, for instance, suggested model modifications regarding (i) Akt contribution to IL-1-stimulated p38 MAPK activation and (ii) insignificant p38 MAPK activation in response to IL-6. In light of the presented results and in conjunction with the detailed model documentations, both models hold great potential for theoretical studies and practical applications. 相似文献
144.
Choquet H Labrune Y De Graeve F Hinney A Hebebrand J Scherag A Lecoeur C Tauber M Balkau B Elliot P Jarvelin MR Walley AJ Besnard P Froguel P Meyre D 《Obesity (Silver Spring, Md.)》2011,19(4):833-839
A recent study suggested that four CD36 polymorphisms (namely rs3211867, rs3211883, rs3211908, and rs1527483) were associated with an increased risk of obesity, an increased BMI and percentage of body fat in European adolescents. We first attempted to confirm these results in three independent case-control genome-wide association studies (GWAS) data totaling 3,509 subjects of French and German origin, but we were unable to find any association of these variants with early onset obesity risk. We then genotyped the four CD36 single-nucleotide polymorphisms (SNPs) in a large population-based study of 4,667 Finnish subjects and we did not replicate any of the recently reported associations with BMI. By combining all available data in a meta-analysis (N = 9,973), we found no evidence for an association of the reported four variants in CD36 with increased obesity risk or increased BMI (0.07 ≤ P values ≤ 0.93). Finally, we assessed the contribution of the full CD36 locus gene variation to obesity risk in 3,509 subjects and we did not detect any significant association with obesity after correction for multiple testing. In summary, we were unable to confirm the recently reported association of variants in CD36 with early onset obesity in populations of European ancestry. 相似文献
145.
Engel KM Schröck K Teupser D Holdt LM Tönjes A Kern M Dietrich K Kovacs P Krügel U Scheidt HA Schiller J Huster D Brockmann GA Augustin M Thiery J Blüher M Stumvoll M Schöneberg T Schulz A 《PloS one》2011,6(12):e29400
G protein-coupled receptors (GPCR) are involved in the regulation of numerous physiological functions. Therefore, GPCR variants may have conferred important selective advantages during periods of human evolution. Indeed, several genomic loci with signatures of recent selection in humans contain GPCR genes among them the X-chromosomally located gene for GPR82. This gene encodes a so-called orphan GPCR with unknown function. To address the functional relevance of GPR82 gene-deficient mice were characterized. GPR82-deficient mice were viable, reproduced normally, and showed no gross anatomical abnormalities. However, GPR82-deficient mice have a reduced body weight and body fat content associated with a lower food intake. Moreover, GPR82-deficient mice showed decreased serum triacylglyceride levels, increased insulin sensitivity and glucose tolerance, most pronounced under Western diet. Because there were no differences in respiratory and metabolic rates between wild-type and GPR82-deficient mice our data suggest that GPR82 function influences food intake and, therefore, energy and body weight balance. GPR82 may represent a thrifty gene most probably representing an advantage during human expansion into new environments. 相似文献
146.
The anaerobic veratrol O-demethylase mediates the transfer of the methyl group of the phenyl methyl ether veratrol to tetrahydrofolate. The primary
methyl group acceptor is the cobalt of a corrinoid protein, which has to be in the +1 oxidation state to bind the methyl group.
Due to the negative redox potential of the cob(II)/cob(I)alamin couple, autoxidation of the cobalt may accidentally occur.
In this study, the reduction of the corrinoid to the superreduced [CoI] state was investigated. The ATP-dependent reduction of the corrinoid protein of the veratrol O-demethylase was shown to be dependent on titanium(III) citrate as electron donor and on an activating enzyme. In the presence
of ATP, activating enzyme, and Ti(III), the redox potential versus the standard hydrogen electrode (E
SHE) of the cob(II)alamin/cob(I)alamin couple in the corrinoid protein was determined to be −290 mV (pH 7.5), whereas E
SHE at pH 7.5 was lower than −450 mV in the absence of either activating enzyme or ATP. ADP, AMP, or GTP could not replace ATP
in the activation reaction. The ATP analogue adenosine-5′-(β,γ-imido)triphosphate (AMP-PNP, 2–4 mM) completely inhibited the
corrinoid reduction in the presence of ATP (2 mM). 相似文献
147.
148.
Almost 10 years ago, microarray technology was established as a new powerful tool for large-scale analysis of gene expression. Soon thereafter the new technology was discovered by toxicologists for the purpose of deciphering the molecular events underlying toxicity, and the term "Toxicogenomics" appeared in scientific literature. Ever since, the toxicology community was fascinated by the multiplicity of sophisticated possibilities toxicogenomics seems to offer: genome-wide analysis of toxicant-induced expression profiles may provide a means for prediction of toxicity prior to classical toxicological endpoints such as histopathology or clinical chemistry. Some researchers even speculated of the classical methods being superfluous before long. It was assumed that by using toxicogenomics it would be possible to classify compounds early in drug development and consequently save animals, time, and money in pre-clinical toxicity studies. Moreover, it seemed within reach to unravel the molecular mechanisms underlying toxicity. The feasibility of bridging data derived from in vitro and in vivo systems, identifying new biomarkers, and comparing toxicological responses "across-species" was also excessively praised. After several years of intensive application of microarray technology in the field of toxicology, not only by the pharmaceutical industry, it is now time to survey its achievements and to question how many of these wishes and promises have really come true. 相似文献
149.
Carotenoid biosynthesis was examined in a phylloplane yeast identified by ITS, 18S and 28S rDNA analysis as a Dioszegia sp. close to D. takashimae. In well-aerated flask or fermentor cultures, this strain produced essentially a single pigment confirmed as the xanthophyll plectaniaxanthin by NMR analysis, at concentrations of 103-175 microgg(-1) biomass dry weight. Detailed studies showed increases in plectaniaxanthin concentrations in the presence of 5 mM hydrogen peroxide (1.8-fold), 50 and 100 microM duroquinone (3.1- and 3.7-fold, respectively), and 2% ethanol (4.9-fold). Whereas oxidative stress is known to enhance the biosynthesis of torularhodin or astaxanthin in other red yeasts where they are associated with an antioxidant function, this is the first report implicating plectaniaxanthin in a similar role. At reduced aeration, biosynthesis of plectaniaxanthin was suppressed and its putative precursor gamma-carotene accumulated. The carotenoid cyclase inhibitor nicotine (5-20 mM) inhibited plectaniaxanthin formation, with lycopene accumulating stoichiometrically. Hydroxy groups at C-1' and C-2' therefore seem to be introduced late in plectaniaxanthin biosynthesis, following cyclization of the beta-ionone ring. 相似文献
150.