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51.
Rollmann SM Magwire MM Morgan TJ Ozsoy ED Yamamoto A Mackay TF Anholt RR 《Nature genetics》2006,38(7):824-829
The abundance of transposable elements and DNA repeat sequences in mammalian genomes raises the question of whether such insertions represent passive evolutionary baggage or may influence the expression of complex traits. We addressed this question in Drosophila melanogaster, in which the effects of single transposable elements on complex traits can be assessed in genetically identical individuals reared in controlled environments. Here we demonstrate that single P-element insertions in the intergenic region between the gustatory receptor 5a (Gr5a, also known as Tre) and trapped in endoderm 1 (Tre1), which encodes an orphan receptor, exert complex pleiotropic effects on fitness traits, including selective nutrient intake, life span, and resistance to starvation and heat stress. Mutations in this region interact epistatically with downstream components of the insulin signaling pathway. Transposon-induced sex-specific and sex-antagonistic effects further accentuate the complex influences that intergenic transposable elements can contribute to quantitative trait phenotypes. 相似文献
52.
Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type 总被引:10,自引:0,他引:10
Lerner-Ellis JP Tirone JC Pawelek PD Doré C Atkinson JL Watkins D Morel CF Fujiwara TM Moras E Hosack AR Dunbar GV Antonicka H Forgetta V Dobson CM Leclerc D Gravel RA Shoubridge EA Coulton JW Lepage P Rommens JM Morgan K Rosenblatt DS 《Nature genetics》2006,38(1):93-100
Methylmalonic aciduria and homocystinuria, cblC type (OMIM 277400), is the most common inborn error of vitamin B(12) (cobalamin) metabolism, with about 250 known cases. Affected individuals have developmental, hematological, neurological, metabolic, ophthalmologic and dermatologic clinical findings. Although considered a disease of infancy or childhood, some individuals develop symptoms in adulthood. The cblC locus was mapped to chromosome region 1p by linkage analysis. We refined the chromosomal interval using homozygosity mapping and haplotype analyses and identified the MMACHC gene. In 204 individuals, 42 different mutations were identified, many consistent with a loss of function of the protein product. One mutation, 271dupA, accounted for 40% of all disease alleles. Transduction of wild-type MMACHC into immortalized cblC fibroblast cell lines corrected the cellular phenotype. Molecular modeling predicts that the C-terminal region of the gene product folds similarly to TonB, a bacterial protein involved in energy transduction for cobalamin uptake. 相似文献
53.
The feeding behaviour of juvenile angelfish (Pterophyllum scalare) has been used as an indicator of their recovery following handling and transfer to a new environment, both with and without conspecifics. Isolated specimens fed less readily than group-housed fish, or those transferred to the test aquaria in groups of three or five, and continued to do so for at least ten days following isolation. Feeding rank-order frequently changed following isolation, suggesting that better foragers may not take the greatest risks in isolation. 相似文献
54.
M J Morgan 《Nature》1992,355(6358):344-346
When we perceive motion on a television or cinema screen, there must be some process that allows us to track moving objects over time: if not, the result would be a conflicting mass of motion signals in all directions. A possible mechanism, suggested by studies of motion displacement in spatially random patterns, is that low-level motion detectors have a limited spatial range, which ensures that they tend to be stimulated over time by the same object. This model predicts that the direction of displacement of random patterns cannot be detected reliably above a critical absolute displacement value (Dmax) that is independent of the size or density of elements in the display. It has been inferred that Dmax is a measure of the size of motion detectors in the visual pathway. Other studies, however, have shown that Dmax increases with element size, in which case the most likely interpretation is that Dmax depends on the probability of false matches between pattern elements following a displacement. These conflicting accounts are reconciled here by showing that Dmax is indeed determined by the spacing between the elements in the pattern, but only after fine detail has been removed by a physiological prefiltering stage: the filter required to explain the data has a similar size to the receptive field of neurons in the primate magnocellular pathway. The model explains why Dmax can be increased by removing high spatial frequencies from random patterns, and simplifies our view of early motion detection. 相似文献
55.
Exo1 and Exo2 proteins stimulate calcium-dependent exocytosis in permeabilized adrenal chromaffin cells. 总被引:17,自引:0,他引:17
In many cell types an increase in cytosolic calcium is the main signal for the exocytotic release of stored secretory components such as hormones and neurotransmitters. The site of action of calcium in exocytosis is not known, neither are the participating molecules. In the case of the intracellular membrane fusions that occur during transport through early stages of the secretory pathway, several cytosolic and peripheral membrane proteins are necessary. Permeabilized cells have been useful in understanding the requirements for calcium and nucleotides in regulated exocytosis and under certain conditions there is leakage of soluble protein components and run-down of the exocytotic response. This system can be used to identify the soluble proteins involved in exocytosis, one candidate in chromaffin cells being annexin II (calpactin). Here we use this assay to identify two other cytosolic protein factors that regulate exocytosis in permeabilized adrenal chromaffin cells, which we term Exo1 and Exo2. Exo1 from brain cytosol resolves on electrophoresis in SDS-polyacrylamide gels as a group of polypeptides of relative molecular mass approximately 30,000 and shares sequence homology with the 14-3-3 family of proteins. The ability of Exo1 to reactivate exocytosis is potentiated by protein kinase C activation and therefore Exo1 may influence the protein kinase C-mediated control of Ca(2+)-dependent exocytosis. 相似文献
56.
Lim JE Jin O Bennett C Morgan K Wang F Trenor CC Fleming MD Andrews NC 《Nature genetics》2005,37(11):1270-1273
Hemoglobin deficit (hbd) mice carry a spontaneous mutation that impairs erythroid iron assimilation but does not cause other defects. Normal delivery of iron to developing erythroid precursors is highly dependent on the transferrin cycle. Through genetic mapping and complementation experiments, we show that the hbd mutation is an in-frame deletion of a conserved exon of the mouse gene Sec15l1, encoding one of two Sec15 proteins implicated in the mammalian exocyst complex. Sec15l1 is linked to the transferrin cycle through its interaction with Rab11, a GTPase involved in vesicular trafficking. We propose that inactivation of Sec15l1 alters recycling of transferrin cycle endosomes and increases the release of transferrin receptor exocytic vesicles. This in turn decreases erythroid iron uptake. Determining the molecular basis of the hbd phenotype provides new insight into the intricate mechanisms necessary for normal erythroid iron uptake and the function of a mammalian exocyst protein. 相似文献
57.
58.
D Zagury G Chaouat D A Morgan G A Voisin 《Comptes rendus des séances de l'Académie des sciences. Série D, Sciences naturelles》1979,288(17):1343-1346
During an alloimmunization, killer cells which lyse target cells only in the presence of a lectin are generated. That these cells, as well as suppressive cells, share immunocytological properties with specific killer cells, leads to the hypothesis that these cells may be concerned with the mechanism of immunosuppression. Two experimental results presented in this paper are consistent with this hypothesis: 1) Spleens from H-2k mice pregnant by H-2d males which bear a high suppressive activity also contain a relatively large number of killer cells having the ability to lyse Concanavalin A treated target cells and 2) supernatants of suppressive systems generated through an MLC block the cytolysis of specific target cells by the bound killer cells. 相似文献
59.
60.