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991.
DHA induces ER stress and growth arrest in human colon cancer cells: associations with cholesterol and calcium homeostasis 总被引:2,自引:0,他引:2
Jakobsen CH Størvold GL Bremseth H Follestad T Sand K Mack M Olsen KS Lundemo AG Iversen JG Krokan HE Schønberg SA 《Journal of lipid research》2008,49(10):2089-2100
Polyunsaturated fatty acids (PUFAs) are normal constituents of the diet, but have properties different from other fatty acids (e.g., through generation of signaling molecules). N-3 PUFAs reduce cancer cell growth, but no unified mechanism has been identified. We show that docosahexaenoic acid (DHA; 22:6 n-3) causes extensive changes in gene expression patterns at mRNA level in the colon cancer cell line SW620. Early changes include unfolded protein response (UPR) and increased levels of phosphorylated eIF2alpha as verified at protein level. The latter is considered a hallmark of endoplasmic reticulum (ER) stress and is abundantly present already after 3 h. It may coordinate many of the downstream changes observed, including signaling pathways for cell cycle arrest/apoptosis, calcium homeostasis, cholesterol metabolism, ubiquitination, and proteasomal degradation. Also, eicosapentaenoic acid (EPA), but not oleic acid (OA), induced key mediators of ER stress and UPR at protein level. Accumulation of esterified cholesterol was not compensated for by increased total levels of cholesterol, and mRNAs for cholesterol biosynthesis as well as de novo synthesis of cholesterol were reduced. These results suggest that cytotoxic effects of DHA are associated with signaling pathways involving lipid metabolism and ER stress. 相似文献
992.
993.
O'Neill CM Morgan C Kirby J Tschoep H Deng PX Brennan M Rosas U Fraser F Hall C Gill S Bancroft I 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2008,116(5):623-634
Quantitative approaches are now widely used to study the genetic architecture of complex traits. However, most studies have
been conducted in single mapping populations, which sample only a fraction of the natural allelic variation available within
a gene pool and can identify only a subset of the loci controlling the traits. To enable the progress towards an understanding
of the global genetic architecture of a broad range of complex traits, we have developed and characterised six new Arabidopsis thaliana recombinant inbred populations. To evaluate the utility of these populations for integrating analyses from multiple populations,
we identified quantitative trait loci (QTL) controlling flowering time in vernalized plants growing in 16 h days. We used
the physical positions of markers to align the linkage maps of our populations with those of six existing populations. We
identified seven QTL in genomic locations coinciding with those identified in previous studies and in addition a further eight
QTL were identified.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
An erratum to this article can be found at 相似文献
994.
Thomas Y Vogel G Wunderli W Suter P Witschi M Koch D Tapparel C Kaiser L 《Applied and environmental microbiology》2008,74(10):3002-3007
Successful control of a viral disease requires knowledge of the different vectors that could promote its transmission among hosts. We assessed the survival of human influenza viruses on banknotes given that billions of these notes are exchanged daily worldwide. Banknotes were experimentally contaminated with representative influenza virus subtypes at various concentrations, and survival was tested after different time periods. Influenza A viruses tested by cell culture survived up to 3 days when they were inoculated at high concentrations. The same inoculum in the presence of respiratory mucus showed a striking increase in survival time (up to 17 days). Similarly, B/Hong Kong/335/2001 virus was still infectious after 1 day when it was mixed with respiratory mucus. When nasopharyngeal secretions of naturally infected children were used, influenza virus survived for at least 48 h in one-third of the cases. The unexpected stability of influenza virus in this nonbiological environment suggests that unusual environmental contamination should be considered in the setting of pandemic preparedness. 相似文献
995.
Victoria Ng Patrick Tang Frances Jamieson Steven J. Drews Shirley Brown Donald E. Low Caroline C. Johnson David N. Fisman 《EcoHealth》2008,5(4):482-490
Legionella species are increasingly recognized as a cause of both healthcare- and community-acquired pneumonia (so-called “Legionnaire’s
disease”). These pathogens are ubiquitous in the environment, but environmental factors in the occurrence of sporadic legionellosis
remain poorly understood. We analyzed all legionellosis cases identified in the Greater Toronto Area of Ontario from 1978
to 2006, and evaluated seasonal and environmental patterns in legionellosis case occurrence by using both negative binomial
models and case-crossover analysis. A total of 837 cases were reported during the study period. After adjusting for seasonal
effects, changes in the local watershed, rather than weather, were the strongest contributors to legionellosis risk. A 3.6-fold
increase (95% confidence interval (CI), 2.4–5.3) in odds of disease was identified with decreasing watershed levels approximately
4 weeks before case-occurrence. We also found a 33% increase (95% CI, 8–64%) in odds of disease with decreasing lake temperature
during the same period and a 34% increase (95% CI, 14–57%) with increasing humidity 5 weeks before case-occurrence. We conclude
that local watershed ecology influences the risk of legionellosis, notwithstanding the availability of advanced water treatment
capacity in Toronto. Enhancement of risk might occur through direct contamination of water sources or via introduction of
micronutrients or commensal organisms into residential and hospital water supplies. These observations suggest testable hypotheses
for future empiric studies. 相似文献
996.
The optimization of a Diels-Alder reaction to prepare a novel ketone bearing a 2,3-dimethylnorbornyl group is presented together with the structure elucidation of the isomers. Employing this new ketone as starting material, derivatives with new woody odor notes as well as attempts to obtain ambery-musky odorants are reported. 相似文献
997.
Free radicals run in lizard families 总被引:1,自引:0,他引:1
In the ageing individual, the production of reactive oxygen species (ROS) accelerates with cell senescence. Depending on the heritability of the underlying processes that determine net ROS levels, this may influence ageing per se and its evolutionary direction and rate of change. In order to understand the inheritance and evolution of net ROS levels in free-ranging lizards, we used flow cytometry together with ROS-sensitive fluorogenic probes to measure ROS in lizard blood cells. We measured basal levels of (i) non-specific ROS (superoxide, singlet oxygen, H2O2 and peroxynitrite), (ii) superoxide specifically and (iii) superoxide after CCCP treatment, which elevated ROS production in the mitochondria. The cumulative level of non-specific ROS was higher in adults than juveniles and superoxide level showed high heritability and variability among families. We suggest that the evolution of ROS dynamics may be ROS species specific and perhaps depend on the relative degree of uni- or biparental inheritance of ROS main regulatory pathways. 相似文献
998.
999.
1000.
The inducible cyclooxygenase isoform (COX-2) is associated with inflammation, tumorigenesis, as well as with physiological events. Despite efforts deployed in order to understand the biology of this multi-faceted enzyme, much remains to be understood. Nucleobindin (Nuc), a ubiquitous Ca(2+)-binding protein, possesses a putative COX-binding domain. In this study, we investigated its expression and subcellular localization in human neutrophils, its affinity for COX-2 as well as its possible impact on PGE(2) biosynthesis. Complementary subcellular localization approaches including nitrogen cavitation coupled to Percoll fractionation, immunofluorescence, confocal and electron microscopy collectively placed Nuc, COX-2, and all of the main enzymes involved in prostanoid synthesis, in the Golgi apparatus and endoplasmic reticulum of human neutrophils. Immunoprecipitation experiments indicated a high affinity between Nuc and COX-2. Addition of human recombinant (hr) Nuc to purified hrCOX-2 dose-dependently caused an increase in PGE(2) biosynthesis in response to arachidonic acid. Co-incubation of Nuc with COX-2-expressing neutrophil lysates also increased their capacity to produce PGE(2). Moreover, neutrophil transfection with hrNuc specifically enhanced PGE(2) biosynthesis. Together, these results identify a COX-2-associated protein which may have an impact in prostanoid biosynthesis. 相似文献