全文获取类型
收费全文 | 298篇 |
免费 | 39篇 |
专业分类
337篇 |
出版年
2021年 | 2篇 |
2020年 | 2篇 |
2018年 | 3篇 |
2017年 | 4篇 |
2015年 | 17篇 |
2014年 | 17篇 |
2013年 | 20篇 |
2012年 | 7篇 |
2011年 | 13篇 |
2010年 | 13篇 |
2009年 | 11篇 |
2008年 | 22篇 |
2007年 | 15篇 |
2006年 | 14篇 |
2005年 | 16篇 |
2004年 | 19篇 |
2003年 | 11篇 |
2002年 | 10篇 |
2001年 | 7篇 |
2000年 | 5篇 |
1999年 | 11篇 |
1998年 | 7篇 |
1997年 | 3篇 |
1996年 | 6篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1988年 | 5篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1985年 | 10篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1977年 | 5篇 |
1975年 | 2篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1970年 | 4篇 |
1967年 | 2篇 |
1965年 | 1篇 |
1950年 | 1篇 |
1921年 | 1篇 |
1920年 | 1篇 |
1919年 | 1篇 |
1917年 | 1篇 |
排序方式: 共有337条查询结果,搜索用时 15 毫秒
1.
A method was developed to optimize simultaneous selection for a quantitative trait with a known QTL within a male and a female line to maximize crossbred performance from a two-way cross. Strategies to maximize cumulative discounted response in crossbred performance over ten generations were derived by optimizing weights in an index of a QTL and phenotype. Strategies were compared to selection on purebred phenotype. Extra responses were limited for QTL with additive and partial dominance effects, but substantial for QTL with over-dominance, for which optimal QTL selection resulted in differential selection in male and female lines to increase the frequency of heterozygotes and polygenic responses. For over-dominant QTL, maximization of crossbred performance one generation at a time resulted in similar responses as optimization across all generations and simultaneous optimal selection in a male and female line resulted in greater response than optimal selection within a single line without crossbreeding. Results show that strategic use of information on over-dominant QTL can enhance crossbred performance without crossbred testing. 相似文献
2.
Pressure-flow relationships in the isolated canine trachea 总被引:1,自引:0,他引:1
3.
Effect of postnatal development on calcium currents and slow charge movement in mammalian skeletal muscle 总被引:16,自引:3,他引:13 下载免费PDF全文
Single- (whole-cell patch) and two-electrode voltage-clamp techniques were used to measure transient (Ifast) and sustained (Islow) calcium currents, linear capacitance, and slow, voltage-dependent charge movements in freshly dissociated fibers of the flexor digitorum brevis (FDB) muscle of rats of various postnatal ages. Peak Ifast was largest in FDB fibers of neonatal (1-5 d) rats, having a magnitude in 10 mM external Ca of 1.4 +/- 0.9 pA/pF (mean +/- SD; current normalized by linear fiber capacitance). Peak Ifast was smaller in FDB fibers of older animals, and by approximately 3 wk postnatal, it was so small as to be unmeasurable. By contrast, the magnitudes of Islow and charge movement increased substantially during postnatal development. Peak Islow was 3.6 +/- 2.5 pA/pF in FDB fibers of 1-5-d rats and increased to 16.4 +/- 6.5 pA/pF in 45-50-d-old rats; for these same two age groups, Qmax, the total mobile charge measurable as charge movement, was 6.0 +/- 1.7 and 23.8 +/- 4.0 nC/microF, respectively. As both Islow and charge movement are thought to arise in the transverse-tubular system, linear capacitance normalized by the area of fiber surface was determined as an indirect measure of the membrane area of the t-system relative to that of the fiber surface. This parameter increased from 1.5 +/- 0.2 microF/cm2 in 2-d fibers to 2.9 +/- 0.4 microF/cm2 in 44-d fibers. The increases in peak Islow, Qmax, and normalized linear capacitance all had similar time courses. Although the function of Islow is unknown, the substantial postnatal increase in its magnitude suggests that it plays an important role in the physiology of skeletal muscle. 相似文献
4.
Photoreactivation of UV-irradiated Legionella pneumophila and other Legionella species. 总被引:1,自引:1,他引:0 下载免费PDF全文
G B Knudson 《Applied microbiology》1985,49(4):975-980
Shortwave UV light was assessed as a feasible modality for the control of Legionnaires disease bacterium in water. The results of this study show that Legionella pneumophila and six other Legionella species are very sensitive to low doses of UV. However, all Legionella species tested effectively countered the germicidal effect of UV when subsequently exposed to photoreactiving light. 相似文献
5.
6.
The relative contributions of ventral blood island mesoderm and dorsal anterior mesoderm to differentiated lineages of hematopoietic cells was assessed by reciprocal grafting of cytogenetically labeled tissues between 67- and 72-hr-old frog embryos (Shumway stages 15–16). Diploid (2N) and triploid (3N) cell populations from hematopoietic organs were distinguished by Feulgen-DNA microdensitometric analysis. Ventral blood island mesoderm appears to contribute an embryonic erythrocyte population that progressively declines during larval development. Dorsal anterior mesoderm appears to contribute a population of precursor cells that gives rise to differentiated lineages of hematopoietic cells found in the thymus, pronephros, mesonephros, spleen, and blood. Histological examination of the developing dorsal anterior area indicates that extensive vascularization is a prominent characteristic of this region. The dorsal aortae and vasculature surrounding the pronephros may be sites where at least one population of hematopoietic cells matures and subsequently enters circulation. 相似文献
7.
For a finite locus model, Markov chain Monte Carlo (MCMC) methods can be used to estimate the conditional mean of genotypic values given phenotypes, which is also known as the best predictor (BP). When computationally feasible, this type of genetic prediction provides an elegant solution to the problem of genetic evaluation under non-additive inheritance, especially for crossbred data. Successful application of MCMC methods for genetic evaluation using finite locus models depends, among other factors, on the number of loci assumed in the model. The effect of the assumed number of loci on evaluations obtained by BP was investigated using data simulated with about 100 loci. For several small pedigrees, genetic evaluations obtained by best linear prediction (BLP) were compared to genetic evaluations obtained by BP. For BLP evaluation, used here as the standard of comparison, only the first and second moments of the joint distribution of the genotypic and phenotypic values must be known. These moments were calculated from the gene frequencies and genotypic effects used in the simulation model. BP evaluation requires the complete distribution to be known. For each model used for BP evaluation, the gene frequencies and genotypic effects, which completely specify the required distribution, were derived such that the genotypic mean, the additive variance, and the dominance variance were the same as in the simulation model. For lowly heritable traits, evaluations obtained by BP under models with up to three loci closely matched the evaluations obtained by BLP for both purebred and crossbred data. For highly heritable traits, models with up to six loci were needed to match the evaluations obtained by BLP. 相似文献
8.
Rachel J. Derscheid Jack M. Gallup Cory J. Knudson Steven M. Varga Drew D. Grosz Albert van Geelen Shannon J. Hostetter Mark R. Ackermann 《PloS one》2013,8(12)
Respiratory syncytial virus (RSV) is the most frequent cause of bronchiolitis in infants and children worldwide. There are currently no licensed vaccines or effective antivirals. The lack of a vaccine is partly due to increased caution following the aftermath of a failed clinical trial of a formalin-inactivated RSV vaccine (FI-RSV) conducted in the 1960’s that led to enhanced disease, necessitating hospitalization of 80% of vaccine recipients and resulting in two fatalities. Perinatal lamb lungs are similar in size, structure and physiology to those of human infants and are susceptible to human strains of RSV that induce similar lesions as those observed in infected human infants. We sought to determine if perinatal lambs immunized with FI-RSV would develop key features of vaccine-enhanced disease. This was tested in colostrum-deprived lambs immunized at 3–5 days of age with FI-RSV followed two weeks later by RSV infection. The FI-RSV-vaccinated lambs exhibited several key features of RSV vaccine-enhanced disease, including reduced RSV titers in bronchoalveolar lavage fluid and lung, and increased infiltration of peribronchiolar and perivascular lymphocytes compared to lambs either undergoing an acute RSV infection or naïve controls; all features of RSV vaccine-enhanced disease. These results represent a first step proof-of-principle demonstration that the lamb can develop altered responses to RSV following FI-RSV vaccination. The lamb model may be useful for future mechanistic studies as well as the assessment of RSV vaccines designed for infants. 相似文献
9.
Nicole M. Chapman Mahmood Y. Bilal Noemi Cruz-Orcutt Cory Knudson Sofia Madinaveitia Jonathan Light Jon C.D. Houtman 《Cellular signalling》2013,25(3):639-650
Toll-like receptor 2 (TLR2) serves as a co-stimulatory receptor for human T cells by enhancing T cell receptor (TCR)-induced cytokine production and proliferation. However, it is unknown where signals from the TCR and TLR2 converge to enhance T cell activation. To address this gap, we examined changes in TCR-induced signaling following concurrent TLR2 activation in human T cells. Both proximal TCR-mediated signaling and early NFκB activation were not enhanced by TCR andTLR2 co-activation, potentially due to the association of TLR2 with TLR10. Instead, TLR2 co-induction did augment Akt and Erk1/Erk2 activation in human T cells. These findings demonstrate that TLR2 activates distinct signaling pathways in human T cells and suggest that alterations in expression of TLR2 co-receptors may contribute to aberrant T cell responses. 相似文献
10.
Kunal Kumar Divya Awasthi Seung-Yub Lee Jason E. Cummings Susan E. Knudson Richard A. Slayden Iwao Ojima 《Bioorganic & medicinal chemistry》2013,21(11):3318-3326
Francisella tularensis is a highly virulent pathogenic bacterium. In order to identify novel potential antibacterial agents against F. tularensis, libraries of trisubstituted benzimidazoles were screened against F. tularensis LVS strain. In a preliminary screening assay, remarkably, 23 of 2,5,6- and 2,5,7-trisubstituted benzimidazoles showed excellent activity exhibiting greater than 90% growth inhibition at 1 μg/mL. Among those hits, 21 compounds showed MIC90 values in the range of 0.35–48.6 μg/mL after accurate MIC determination. In ex vivo efficacy assays, four of these compounds exhibited 2–3 log reduction in colony forming units (CFU) per mL at concentrations of 10 and 50 μg/mL. 相似文献