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101.
An inhibitor of microRNA-122 reduces viral load in chimpanzees that are chronically infected with hepatitis C virus, suggesting that such an approach might have therapeutic potential in humans. 相似文献
102.
I Dawidson R Simonsen S Aggarwal L Coorpender K Diller R Rajotte P Raskin H Redman J Rosenstock 《Cryobiology》1988,25(2):83-93
Human fetal pancreata (HFP) were obtained from dilatation and extraction aborted fetuses of 11-18 weeks' gestation. The pancreas was excised under sterile conditions and kept in culture medium at 4 degrees C, prior to stepwise digestion into 50- to 150-micron fragments. The fragmented pieces were allowed to sediment by gravity, then transferred to tissue culture for 24-48 h, and cryopreserved. The freeze-thaw protocol used stepwise equilibration with dimethyl sulfoxide, nucleation of the sample at -10 degrees C, and a slow cooling rate of 0.25 degrees C/min to -40 degrees C, followed by submersion in liquid nitrogen (-196 degrees C). Rapid thawing at 300 degrees C/min from -196 degrees C was employed. Both fresh and frozen-thawed HFP fragments appeared viable as judged by light and electron microscopy, and secreted insulin in a perifusion system upon stimulation with glucose (28 mM) and theophylline (10 mM) or glucose (2.8 mM) and theophylline (10 mM). Six patients with Type I insulin-dependent diabetes mellitus, already requiring immunosuppression for a kidney transplant, had intraportal injection of 20 cryopreserved-thawed and pooled HFP fragments. Up to the 1-year post-transplant follow-up, there has been no evidence of in vivo insulin or C-peptide production. The usefulness of cryopreserved human fetal pancreata as a source of insulin-producing tissue for diabetic patients, therefore, remains to be demonstrated. 相似文献
103.
C Schuck-Paim C Viboud L Simonsen MA Miller FE Moura RM Fernandes ML Carvalho WJ Alonso 《PloS one》2012,7(8):e41918
Although it is in the Tropics where nearly half of the world population lives and infectious disease burden is highest, little is known about the impact of influenza pandemics in this area. We investigated the mortality impact of the 2009 influenza pandemic relative to mortality rates from various outcomes in pre-pandemic years throughout a wide range of latitudes encompassing the entire tropical, and part of the subtropical, zone of the Southern Hemisphere (+5(°)N to -35(°)S) by focusing on a country with relatively uniform health care, disease surveillance, immunization and mitigation policies: Brazil. To this end, we analyzed laboratory-confirmed deaths and vital statistics mortality beyond pre-pandemic levels for each Brazilian state. Pneumonia, influenza and respiratory mortality were significantly higher during the pandemic, affecting predominantly adults aged 25 to 65 years. Overall, there were 2,273 and 2,787 additional P&I- and respiratory deaths during the pandemic, corresponding to a 5.2% and 2.7% increase, respectively, over average pre-pandemic annual mortality. However, there was a marked spatial structure in mortality that was independent of socio-demographic indicators and inversely related with income: mortality was progressively lower towards equatorial regions, where low or no difference from pre-pandemic mortality levels was identified. Additionally, the onset of pandemic-associated mortality was progressively delayed in equatorial states. Unexpectedly, there was no additional mortality from circulatory causes. Comparing disease burden reliably across regions is critical in those areas marked by competing health priorities and limited resources. Our results suggest, however, that tropical regions of the Southern Hemisphere may have been disproportionally less affected by the pandemic, and that climate may have played a key role in this regard. These findings have a direct bearing on global estimates of pandemic burden and the assessment of the role of immunological, socioeconomic and environmental drivers of the transmissibility and severity of this pandemic. 相似文献
104.
Charu V Viboud C Simonsen L Sturm-Ramirez K Shinjoh M Chowell G Miller M Sugaya N 《PloS one》2011,6(11):e26282
Background
The historical Japanese influenza vaccination program targeted at schoolchildren provides a unique opportunity to evaluate the indirect benefits of vaccinating high-transmitter groups to mitigate disease burden among seniors. Here we characterize the indirect mortality benefits of vaccinating schoolchildren based on data from Japan and the US.Methods
We compared age-specific influenza-related excess mortality rates in Japanese seniors aged ≥65 years during the schoolchildren vaccination program (1978–1994) and after the program was discontinued (1995–2006). Indirect vaccine benefits were adjusted for demographic changes, socioeconomics and dominant influenza subtype; US mortality data were used as a control.Results
We estimate that the schoolchildren vaccination program conferred a 36% adjusted mortality reduction among Japanese seniors (95%CI: 17–51%), corresponding to ∼1,000 senior deaths averted by vaccination annually (95%CI: 400–1,800). In contrast, influenza-related mortality did not change among US seniors, despite increasing vaccine coverage in this population.Conclusions
The Japanese schoolchildren vaccination program was associated with substantial indirect mortality benefits in seniors. 相似文献105.
Genomic haplotype blocks may not accurately reflect spatial variation in historic recombination intensity 总被引:1,自引:0,他引:1
Recently, genomic data have revealed a "block-like" structure of haplotype diversity on human chromosomes. This structure is anticipated to facilitate gene mapping studies, because strong associations among loci within a block may allow haplotype variation to be tagged with a limited number of markers. But its usefulness to mapping efforts depends on the consistency of the block structure within and among populations, which in turn depends on how the block structure arises. Recombination hot spots are generally thought to underlie the block structure, but haplotype blocks can also develop stochastically under random recombination, in which case the block structure will show limited consistency among populations. Using coalescent models, which we upscaled to simulate the evolution of haplotypes with many markers at fixed distances, we show that the relationship between block boundaries and historic recombination intensity may be surprisingly weak. The majority of historic recombinations do not leave a footprint in present-day linkage disequilibrium patterns, and the block structure is sensitive to factors that affect the timing of recombination relative to marker mutation events in the genealogy, such as marker frequency bias and historic population size changes. Our results give insight into the potential of stochastic events to affect haplotype block structure, which can limit the usefulness of the block structure to mapping studies. 相似文献
106.
Phosphoinositide 3 kinases (PI3Ks)*Abbreviation used in this paper: PI3K, phosphoinositide 3 kinase. are known as regulators of phagocytosis. Recent results demonstrate that class I and III PI3Ks act consecutively in phagosome formation and maturation, and that their respective products, phosphatidylinositol 3,4,5-trisphosphate (PI[3,4,5]P(3)) and phosphatidylinositol 3-phosphate (PI[3]P), accumulate transiently at different stages. Phagosomes containing Mycobacterium tuberculosis do not acquire the PI(3)P-binding protein EEA1, which is required for phagosome maturation. This suggests a possible mechanism of how this microorganism evades degradation in phagolysosomes. 相似文献
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