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排序方式: 共有621条查询结果,搜索用时 31 毫秒
81.
Poulsen HE Specht E Broedbaek K Henriksen T Ellervik C Mandrup-Poulsen T Tonnesen M Nielsen PE Andersen HU Weimann A 《Free radical biology & medicine》2012,52(8):1353-1361
The past decade has provided exciting insights into a novel class of central (small) RNA molecules intimately involved in gene regulation. Only a small percentage of our DNA is translated into proteins by mRNA, yet 80% or more of the DNA is transcribed into RNA, and this RNA has been found to encompass various classes of novel regulatory RNAs, including, e.g., microRNAs. It is well known that DNA is constantly oxidized and repaired by complex genome maintenance mechanisms. Analogously, RNA also undergoes significant oxidation, and there are now convincing data suggesting that oxidation, and the consequent loss of integrity of RNA, is a mechanism for disease development. Oxidized RNA is found in a large variety of diseases, and interest has been especially devoted to degenerative brain diseases such as Alzheimer disease, in which up to 50-70% of specific mRNA molecules are reported oxidized, whereas other RNA molecules show virtually no oxidation. The iron-storage disease hemochromatosis exhibits the most prominent general increase in RNA oxidation ever observed. Oxidation of RNA primarily leads to strand breaks and to oxidative base modifications. Oxidized mRNA is recognized by the ribosomes, but the oxidation results in ribosomal stalling and dysfunction, followed by decreased levels of functional protein as well as the production of truncated proteins that do not undergo proper folding and may result in protein aggregation within the cell. Ribosomal dysfunction may also signal apoptosis by p53-independent pathways. There are very few reports on interventions that reduce RNA oxidation, one interesting observation being a reduction in RNA oxidation by ingestion of raw olive oil. High urinary excretion of 8-oxo-guanosine, a biomarker for RNA oxidation, is highly predictive of death in newly diagnosed type 2 diabetics; this demonstrates the clinical relevance of RNA oxidation. Taken collectively the available data suggest that RNA oxidation is a contributing factor in several diseases such as diabetes, hemochromatosis, heart failure, and β-cell destruction. The mechanism involves free iron and hydrogen peroxide from mitochondrial dysfunction that together lead to RNA oxidation that in turn gives rise to truncated proteins that may cause aggregation. Thus RNA oxidation may well be an important novel contributing mechanism for several diseases. 相似文献
82.
Robert Smith Harald T. Johansen Hilde Nilsen Mads H. Haugen Solveig J. Pettersen Gunhild M. Mælandsmo Magnus Abrahamson Rigmor Solberg 《Biochimie》2012
Legumain, an asparaginyl endopeptidase, is up-regulated in tumour and tumour-associated cells, and is linked to the processing of cathepsin B, L, and proMMP-2. Although legumain is mainly localized to the endosomal/lysosomal compartments, legumain has been reported to be localized extracellularly in the tumour microenvironment and associated with extracellular matrix and cell surfaces. The most potent endogenous inhibitor of legumain is cystatin E/M, which is a secreted protein synthesised with an export signal. Therefore, we investigated the cellular interplay between legumain and cystatin E/M. As a cell model, HEK293 cells were transfected with legumain cDNA, cystatin E/M cDNA, or both, and over-expressing monoclonal cell lines were selected (termed M38L, M4C, and M3CL, respectively). Secretion of prolegumain from M38L cells was inhibited by treatment with brefeldin A, whereas bafilomycin A1 enhanced the secretion. Cellular processing of prolegumain to the 46 and 36 kDa enzymatically active forms was reduced by treatment with either substance alone. M38L cells showed increased, but M4C cells decreased, cathepsin L processing suggesting a crucial involvement of legumain activity. Furthermore, we observed internalization of cystatin E/M and subsequently decreased intracellular legumain activity. Also, prolegumain was shown to internalize followed by increased intracellular legumain processing and activation. In addition, in M4C cells incomplete processing of the internalized prolegumain was observed, as well as nuclear localized cystatin E/M. Furthermore, auto-activation of secreted prolegumain was inhibited by cystatin E/M, which for the first time shows a regulatory role of cystatin E/M in controlling both intra- and extracellular legumain activity. 相似文献
83.
Breiting LB Henriksen TF Kalialis LV Gramkow C Høyer AP 《Plastic and reconstructive surgery》2012,130(2):273-281
84.
Haugen TA Tønnessen E Seiler SK 《Journal of strength and conditioning research / National Strength & Conditioning Association》2012,26(2):473-479
The difference is in the start: impact of timing and start procedure on sprint running performance. The purpose of this study was to compare different sprint start positions and to generate correction factors between popular timing triggering methods on 40-m/40-yd sprint time. Fourteen female athletes (17 ± 1 years), personal best 100 m: 13.26 (±0.68) seconds and 11 male athletes (20 ± 5 years), personal best 100 m: 11.58 (±0.74) seconds participated. They performed 2 series of 3 40-m sprints in randomized order: (a) start from the block, measured by means of Brower audio sensor (BAS) and Dartfish video timing (DVT), (b) 3-point start, measured by using hand release pod (HR) and DVT, and (c) standing start, triggered by both photocell across starting line (SFC), and foot release (FR) plus DVT. Video analysis was performed by 2 independent observers and averaged. Simultaneous measurements at national athletics competitions demonstrated that DVT and BAS were equivalent to Omega Timing within the limits of precision of video timing (±0.01 seconds). Hand and floor timer triggering showed small but significant biases compared with movement captured from video (0.02-0.04 seconds), presumably because of sensitivity of pressure thresholds. Coefficient of variation for test-retest timing using different starting positions ranged from 0.7 to 1.0%. Compared with block starts reacting to gunfire, HR, SFC, and FR starts yielded 0.17 ± 0.09, 0.27 ± 0.12, and 0.69 ± 0.11 second faster times, respectively, over 40 m (all p < 0.001) because of inclusion or exclusion of reaction time, plus momentum, and body position differences at trigger moment. Correction factors for the conversion of 40 m/40 yd and 40 yd/40 m were 0.92 and 1.08, respectively. The correction factors obtained from this study may facilitate more meaningful comparisons of published sprint performances. 相似文献
85.
Kohno T Ichikawa H Totoki Y Yasuda K Hiramoto M Nammo T Sakamoto H Tsuta K Furuta K Shimada Y Iwakawa R Ogiwara H Oike T Enari M Schetter AJ Okayama H Haugen A Skaug V Chiku S Yamanaka I Arai Y Watanabe S Sekine I Ogawa S Harris CC Tsuda H Yoshida T Yokota J Shibata T 《Nature medicine》2012,18(3):375-377
86.
87.
Atrial fibrillation, a common cardiac arrhythmia, often progresses unfavourably: in patients with long-term atrial fibrillation, fibrillatory episodes are typically of increased duration and frequency of occurrence relative to healthy controls. This is due to electrical, structural, and contractile remodeling processes. We investigated mechanisms of how electrical and structural remodeling contribute to perpetuation of simulated atrial fibrillation, using a mathematical model of the human atrial action potential incorporated into an anatomically realistic three-dimensional structural model of the human atria. Electrical and structural remodeling both shortened the atrial wavelength--electrical remodeling primarily through a decrease in action potential duration, while structural remodeling primarily slowed conduction. The decrease in wavelength correlates with an increase in the average duration of atrial fibrillation/flutter episodes. The dependence of reentry duration on wavelength was the same for electrical vs. structural remodeling. However, the dynamics during atrial reentry varied between electrical, structural, and combined electrical and structural remodeling in several ways, including: (i) with structural remodeling there were more occurrences of fragmented wavefronts and hence more filaments than during electrical remodeling; (ii) dominant waves anchored around different anatomical obstacles in electrical vs. structural remodeling; (iii) dominant waves were often not anchored in combined electrical and structural remodeling. We conclude that, in simulated atrial fibrillation, the wavelength dependence of reentry duration is similar for electrical and structural remodeling, despite major differences in overall dynamics, including maximal number of filaments, wave fragmentation, restitution properties, and whether dominant waves are anchored to anatomical obstacles or spiralling freely. 相似文献
88.
Developmental pathways may evolve to optimize alternative phenotypes across environments. However, the maintenance of such adaptive plasticity under relaxed selection has received little study. We compare the expression of life-history traits across two developmental pathways in two populations of the butterfly Pararge aegeria where both populations express a diapause pathway but one never expresses direct development in nature. In the population with ongoing selection on both pathways, the difference between pathways in development time and growth rate was larger, whereas the difference in body size was smaller compared with the population experiencing relaxed selection on one pathway. This indicates that relaxed selection on the direct pathway has allowed life-history traits to drift towards values associated with lower fitness when following this pathway. Relaxed selection on direct development was also associated with a higher degree of genetic variation for protandry expressed as within-family sexual dimorphism in growth rate. Genetic correlations for larval growth rate across sexes and pathways were generally positive, with the notable exception of correlation estimates that involved directly developing males of the population that experienced relaxed selection on this pathway. We conclude that relaxed selection on one developmental pathway appears to have partly disrupted the developmental regulation of life-history trait expression. This in turn suggests that ongoing selection may be responsible for maintaining adaptive developmental regulation along alternative developmental pathways in these populations. 相似文献
89.
90.
Rebound effects of price differences 总被引:1,自引:1,他引:0
Joan Thiesen Torben S. Christensen Thomas G. Kristensen Rikke D. Andersen Brit Brunoe Trine K. Gregersen Mikkel Thrane Bo P. Weidema 《The International Journal of Life Cycle Assessment》2008,13(2):104-114
Goal, Scope and Background Traditionally, comparative life cycle assessments (LCA) have not considered rebound effects, for instance in case of significant
price differences among the compared products. No justifications have been made for this delimitation in scope. This article
shows that price differences and the consequent effects of marginal consumer expenditure may influence the conclusions of
comparative LCA significantly. We also show that considerations about rebound effects of price differences can be included
in LCAs.
Methods The direct rebound effect of a price difference is marginal consumption. Based on statistical data on private consumption
in different income groups (Statistics Denmark 2005a, 2005b), the present article provides an estimate of how an average Danish
household will spend an additional 1 DKK for further consumer goods, when the household has gained money from choosing a cheaper
product alternative. The approach is to use marginal income changes and the following changes in consumption patterns as an
expression for marginal consumption. Secondly, the environmental impact potentials related to this marginal consumption are
estimated by the use of environmental impact intensity data from an IO-LCA database (Weidema et al. 2005). Finally, it is
discussed whether, and in which ways the conclusions of comparative LCAs can be affected by including the price difference
between product alternatives. This is elucidated in a case study of a comparative LCA screening of two different kinds of
Danish cheese products (Fricke et al. 2004).
Results Car purchase and driving, use and maintenance of dwelling, clothing purchase and insurance constitutes the largest percentages
of the marginal consumption. In a case study of two cheeses, the including the impact potentials related to the price difference
results in significant changes in the total impact potentials. Considering the relatively small price difference of the two
products, it is likely also to have a significant influence on the results of comparative LCAs more generally.
Discussion The influence of marginal consumption in comparative LCAs is relevant to consider in situations with large differences in
the price of the product alternatives being compared, and in situations with minor differences in the impact potentials related
to the alternatives. However, different uncertainties are linked to determining the pattern for marginal consumption and the
environmental impact potential related to this. These are first of all related to the method used, but also include inaccurate
data of consumption in households, aggregation and weighting of income groups, aggregation of product groups, estimation and
size of the price difference, and the general applicability of the results.
Conclusion Incorporating marginal consumption in consequential LCAs is possible in practice. In the case study used, including the rebound
effects of the price difference has a significant influence on the result of the comparative LCA, as the result for the impact
categories acidification and nutrient enrichment changes in favour of the expensive product.
Recommendations and Perspectives It is recommended that the rebound effects of price differences should be included more frequently in LCAs. In order to ensure
this, further research in marginal consumption and investment patterns and IO data for different countries or regions is required.
Furthermore, this study does not consider the economic distributional consequences of buying an expensive product instead
of a cheaper product (e.g. related to how the profit is spent by those who provided the product). It should also be noted,
that more expensive products not necessarily result in less consumption, as those who provided the product also will spend
the money they have earned from the sale. Ideally, these consequences should also be further investigated. Likewise, the development
of databases to include marginal consumption in PC-tools is needed. In general, considerations of marginal consumption would
favour expensive product alternatives, depending, however, on the type of consumer.
ESS-Submission Editor: Dr. David Hunkeler (david.hunkeler@aquaplustech.ch) 相似文献