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991.
Christian H. C. A. Henning Nana Zarnekow Johannes Hedtrich Sascha Stark Kathrin Türk Matthias Laudes 《PloS one》2014,9(4)
Objective
The aim of the present study was to examine to what extent different social network mechanisms are involved in the pathogenesis of obesity and insulin-resistance.Design
We used nonparametric and parametric regression models to analyse whether individual BMI and HOMA-IR are determined by social network characteristics.Subjects and Methods
A total of 677 probands (EGO) and 3033 social network partners (ALTER) were included in the study. Data gathered from the probands include anthropometric measures, HOMA-IR index, health attitudes, behavioural and socio-economic variables and social network data.Results
We found significant treatment effects for ALTERs frequent dieting (p<0.001) and ALTERs health oriented nutritional attitudes (p<0.001) on EGO''s BMI, establishing a significant indirect network effect also on EGO''s insulin resistance. Most importantly, we also found significant direct social network effects on EGO''s insulin resistance, evidenced by an effect of ALTERs frequent dieting (p = 0.033) and ALTERs sport activities (p = 0.041) to decrease EGO''s HOMA-IR index independently of EGO''s BMI.Conclusions
Social network phenomena appear not only to be relevant for the spread of obesity, but also for the spread of insulin resistance as the basis for type 2 diabetes. Attitudes and behaviour of peer groups influence EGO''s health status not only via social mechanisms, but also via socio-biological mechanisms, i.e. higher brain areas might be influenced not only by biological signals from the own organism, but also by behaviour and knowledge from different human individuals. Our approach allows the identification of peer group influence controlling for potential homophily even when using cross-sectional observational data. 相似文献992.
993.
994.
Kristin A. Marks Phillip M. Marvyn Juan J. Aristizabal Henao Ryan M. Bradley Ken D. Stark Robin E. Duncan 《Genes & nutrition》2015,10(6)
We investigated the effect of short-term fasting on coordinate changes in the fatty acid composition of adipose triacylglycerol (TAG), serum non-esterified fatty acids (NEFA), liver TAG, and serum TAG and phospholipids in mice fed ad libitum or fasted for 16 h overnight. In contrast to previous reports under conditions of maximal lipolysis, adipose tissue TAG was not preferentially depleted of n-3 PUFA or any specific fatty acids, nor were there any striking changes in the serum NEFA composition. Short-term fasting did, however, increase the hepatic proportion of n-3 PUFA, and almost all individual species of n-3 PUFA showed relative and absolute increases. The relative proportion of n-6 PUFA in liver TAG also increased but to a lesser extent, resulting in a significant decrease in the n-6:n-3 PUFA ratio (from 14.3 ± 2.54 to 9.6 ± 1.20), while the proportion of MUFA decreased significantly and SFA proportion did not change. Examination of genes involved in PUFA synthesis suggested that hepatic changes in the elongation and desaturation of precursor lipids could not explain this effect. Rather, an increase in the expression of fatty acid transporters specific for 22:6n-3 and other long-chain n-3 and n-6 PUFA likely mediated the observed hepatic enrichment. Analysis of serum phospholipids indicated a specific increase in the concentration of 22:6n-3 and 16:0, suggesting increased specific synthesis of DHA-enriched phospholipid by the liver for recirculation. Given the importance of blood phospholipid in distributing DHA to neural tissue, these findings have implications for understanding the adipose–liver–brain axis in n-3 PUFA metabolism.
Electronic supplementary material
The online version of this article (doi:10.1007/s12263-015-0490-2) contains supplementary material, which is available to authorized users. 相似文献995.
Xiaokun Wang Yong Huang Sabah Jastaneiah Shoumyo Majumdar Jin U. Kang Samuel C. Yiu Walter Stark Jennifer H. Elisseeff 《PloS one》2015,10(9)
Collagen crosslinking is a relatively new treatment for structural disorders of corneal ectasia, such as keratoconus. However, there is a lack of animal models of keratoconus, which has been an obstacle for carefully analyzing the mechanisms of crosslinking and evaluating new therapies. In this study, we treated rabbit eyes with collagenase and chondroitinase enzymes to generate ex vivo corneal ectatic models that simulate the structural disorder of keratoconus. The models were then used to evaluate the protective effect of soluble collagen in the UVA crosslinking system. After enzyme treatment, the eyes were exposed to riboflavin/UVA crosslinking with and without soluble type I collagen. Corneal morphology, collagen ultrastructure, and thermal stability were evaluated before and after crosslinking. Enzyme treatments resulted in corneal curvature changes, collagen ultrastructural damage, decreased swelling resistance and thermal stability, which are similar to what is observed in keratoconus eyes. UVA crosslinking restored swelling resistance and thermal stability, but ultrastructural damage were found in the crosslinked ectatic corneas. Adding soluble collagen during crosslinking provided ultrastructural protection and further enhanced the swelling resistance. Therefore, UVA crosslinking on the ectatic model mimicked typical clinical treatment for keratoconus, suggesting that this model replicates aspects of human keratoconus and could be used for investigating experimental therapies and treatments prior to translation. 相似文献
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997.
Colleen R. Reczek Matthias Szabolcs Jeremy M. Stark Thomas Ludwig Richard Baer 《The Journal of cell biology》2013,201(5):693-707
The CtIP protein facilitates homology-directed repair (HDR) of double-strand DNA breaks (DSBs) by initiating DNA resection, a process in which DSB ends are converted into 3′-ssDNA overhangs. The BRCA1 tumor suppressor, which interacts with CtIP in a phospho-dependent manner, has also been implicated in DSB repair through the HDR pathway. It was recently reported that the BRCA1–CtIP interaction is essential for HDR in chicken DT40 cells. To examine the role of this interaction in mammalian cells, we generated cells and mice that express Ctip polypeptides (Ctip-S326A) that fail to bind BRCA1. Surprisingly, isogenic lines of Ctip-S326A mutant and wild-type cells displayed comparable levels of HDR function and chromosomal stability. Although Ctip-S326A mutant cells were modestly sensitive to topoisomerase inhibitors, mice expressing Ctip-S326A polypeptides developed normally and did not exhibit a predisposition to cancer. Thus, in mammals, the phospho-dependent BRCA1–CtIP interaction is not essential for HDR-mediated DSB repair or for tumor suppression. 相似文献
998.
Florian Hauer Christoph Gerle Jan-Martin Kirves Holger Stark 《Journal of structural biology》2013,181(2):149-154
One of the major methodological challenges in single particle electron microscopy is obtaining initial reconstructions which represent the structural heterogeneity of the dataset. Random Conical Tilt and Orthogonal Tilt Reconstruction techniques in combination with 3D alignment and classification can be used to obtain initial low-resolution reconstructions which represent the full range of structural heterogeneity of the dataset. In order to achieve statistical significance, however, a large number of 3D reconstructions, and, in turn, a large number of tilted image pairs are required. The extraction of single particle tilted image pairs from micrographs can be tedious and time-consuming, as it requires intensive user input even for semi-automated approaches. To overcome the bottleneck of manual selection of a large number of tilt pairs, we developed an algorithm for the correlation of single particle images from tilted image pairs in a fully automated and user-independent manner. The algorithm reliably correlates correct pairs even from noisy micrographs. We further demonstrate the applicability of the algorithm by using it to obtain initial references both from negative stain and unstained cryo datasets. 相似文献
999.
Ling-Jie Gao J. Stephan Schwed Lilia Weizel Steven De Jonghe Holger Stark Piet Herdewijn 《Bioorganic & medicinal chemistry letters》2013,23(1):132-137
Starting from a known H4R ligand based on a pyrimidine skeleton, a series of novel analogues based on a pyrrolo[2,3-d]pyrimidine scaffold have been prepared. Whereas the original pyrimidine congener shows good affinity at hH4R (Ki = 0.5 μM), its lacks selectivity with a Ki value for the hH3R of 1 μM. Within the newly synthesized pyrrolo[2,3-d]pyrimidines, several congeners show Ki values of less than 1 μM at the hH4R and show a much improved selectivity profile. Therefore, these series represent an interesting starting point for the discovery of novel hH4R ligands. 相似文献
1000.