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51.
C H Hsu T W Kurtz H G Preuss J M Weller 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1975,149(2):470-472
The radioactive microsphere technique is a simple method for measurement of RBF and intrarenal blood flow distribution in the rat that does not require surgical manipulation of the kidney or general anesthesia. The results are reproducible and compatible with other established techniques. 相似文献
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Selective genotyping to detect quantitative trait loci affecting multiple traits: interval mapping analysis 总被引:3,自引:0,他引:3
Y. I. Ronin A. B. Korol J. I. Weller 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1998,97(7):1169-1178
Segregating quantitative trait loci can be detected via linkage to genetic markers. By selectively genotyping individuals
with extreme phenotypes for the quantitative trait, the power per individual genotyped is increased at the expense of the
power per individual phenotyped, but linear-model estimates of the quantitative-locus effect will be biased. The properties
of single- and multiple-trait maximum-likelihood estimates of quantitative-loci parameters derived from selectively genotyped
samples were investigated using Monte-Carlo simulations of backcross populations. All individuals with trait records were
included in the analyses. All quantitative-locus parameters and the residual correlation were unbiasedly estimated by multiple-trait
maximum-likelihood methodology. With single-trait maximum-likelihood, unbiased estimates for quantitative-locus effect and
location, and the residual variance, were obtained for the trait under selection, but biased estimates were derived for a
correlated trait that was analyzed separately. When an effect of the QTL was simulated only on the trait under selection,
a “ghost” effect was also found for the correlated trait. Furthermore, if an effect was simulated only for the correlated
trait, then the statistical power was less than that obtained with a random sample of equal size. With multiple-trait analyses,
the power of quantitative-trait locus detection was always greater with selective genotyping.
Received: 23 February 1998 / Accepted: 15 May 1998 相似文献
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Direct control of exocytosis by receptor-mediated activation of the heterotrimeric GTPases Gi and G(o) or by the expression of their active G alpha subunits. 总被引:2,自引:4,他引:2 下载免费PDF全文
J Lang I Nishimoto T Okamoto R Regazzi C Kiraly U Weller C B Wollheim 《The EMBO journal》1995,14(15):3635-3644
The exocytotic release of potent hormones is a tightly controlled process. Its direct regulation without the involvement of second messengers would ensure rapid signal processing. In streptolysin O-permeabilized insulin-secreting cells, a preparation allowing dialysis of cytosolic macromolecules, activation of alpha 2-adrenergic receptors caused pertussis toxin-sensitive inhibition of calcium-induced exocytosis. This inhibition was mimicked very efficiently by the use of specific receptor-mimetic peptides, indicating the involvement of Gi and, to a lesser extent, of G(o). The regulation was exerted beyond the ATP-dependent step of exocytosis. In addition, low nanomolar amounts of pre-activated Gi/G(o) directly inhibited exocytosis. As transient overexpression of constitutively active mutants of G alpha i1, G alpha i2, G alpha i3 and G alpha o2 but not of G alpha o1 reproduced this regulation, the G alpha subunit alone is sufficient to induce inhibition. These results define exocytosis as an effector for heterotrimeric G-proteins and delineate the properties of the transduction pathway. 相似文献
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Proteasome inhibitor-induced apoptosis of glioma cells involves the processing of multiple caspases and cytochrome c release 总被引:4,自引:0,他引:4
Wagenknecht B Hermisson M Groscurth P Liston P Krammer PH Weller M 《Journal of neurochemistry》2000,75(6):2288-2297
The proteasome is a multiprotein complex that is involved in the intracellular protein degradation in eukaryotes. Here, we show that human malignant glioma cells are susceptible to apoptotic cell death induced by the proteasome inhibitors, MG132 and lactacystin. The execution of the apoptotic death program involves the processing of caspases 2, 3, 7, 8, and 9. Apoptosis is inhibited by ectopic expression of X-linked inhibitor of apoptosis (XIAP) and by coexposure to the broad-spectrum caspase inhibitor, benzoyl-VAD-fluoromethyl ketone (zVAD-fmk), but not by the preferential caspase 8 inhibitor, crm-A. It is interesting that specific morphological alterations induced by proteasome inhibition, such as dilated rough endoplasmic reticulum and the formation of cytoplasmic vacuoles and dense mitochondrial deposits, are unaffected by zVAD-fmk. Apoptosis is also inhibited by ectopic expression of Bcl-2 or by an inhibitor of protein synthesis, cycloheximide. Further, cytochrome c release and disruption of mitochondrial membrane potential are prominent features of apoptosis triggered by proteasome inhibition. Bcl-2 is a stronger inhibitor of cytochrome c release than zVAD-fmk. XIAP and crm-A fail to modulate cytochrome c release. These data place cytochrome c release downstream of Bcl-2 activity but upstream of XIAP- and crm-A-sensitive caspases. The partial inhibition of cytochrome c release by zVAD-fmk indicates a positive feedback loop that may involve cytochrome c release and zVAD-fmk-sensitive caspases. Finally, death ligand/receptor interactions, including the CD95/CD95 ligand system, do not mediate apoptosis induced by proteasome inhibition in human malignant glioma cells. 相似文献
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