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1.
A possible interaction between Cd2+ and Ca2+ as a component in Cd2+-induced insulin release was investigated in beta cells isolated from obese hyperglycemic mice. The glucose stimulated Cd2+ uptake was dependent on the concentration of sugar. This uptake was sigmoidal with a Km for glucose of about 5 mM and was suppressed by both 50 microM of the voltage-activated Ca2+ channel blocker D-600 and 12 mM Mg2+. In the presence of 8 mM glucose 5 microM Cd2+ evoked a prompt and sustained stimulatory response, corresponding to about 3-fold of the insulin release obtained in the absence of the ion. Whereas 5 microM Cd2+ was without effect on the glucose-stimulated 45Ca efflux in the presence of extracellular Ca2+, 40 microM inhibited it. At a concentration of 5 microM, Cd2+ had no effect on the resting membrane potential or the depolarization evoked by either glucose or K+. In the absence of extracellular Ca2+ there was only a modest stimulation of 45Ca efflux by 5 microM Cd2+. Studies of the ambient free Ca2+ concentration maintained by permeabilized cells also indicate that 5 microM Cd2+ do not mobilize intracellularly bound Ca2+ to any great extent. On the contrary, at this concentration, Cd2+ even suppressed inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release. The present study suggests that Cd2+ stimulates insulin release by a direct mechanism which does not involve an increase in cytoplasmic free Ca2+ concentration.  相似文献   
2.
Pancreatic beta-cells isolated from obese-hyperglycaemic mice released intracellular Ca2+ in response to carbamoylcholine, an effect dependent on the presence of glucose. The effective Ca2+ concentration reached was sufficient to evoke a transient release of insulin. When the cells were deficient in Ca2+, the Ca2+ pool sensitive to carbamoylcholine stimulation was equivalent to that released by ionomycin. Unlike intact cells, cells permeabilized by high-voltage discharges failed to generate either inositol 1,4,5-triphosphate (InsP3) or to release Ca2+ after exposure to carbamoylcholine. However, the permeabilized cells released insulin sigmoidally in response to increasing concentrations of Ca2+. Also in the absence of functional mitochondria these cells exhibited a large ATP-dependent buffering of Ca2+, enabling the maintenance of an ambient Ca2+ concentration corresponding to about 150 nM even after several additional pulses of Ca2+. InsP3, maximally effective at 6 microM, promoted a rapid and pronounced release of Ca2+. The InsP3-sensitive Ca2+ pool was rapidly filled and lost its Ca2+ late after ATP depletion. The transient nature of the Ca2+ signal was not overcome by repetitive additions of InsP3. It was possible to restore the response to InsP3 after a delay of approx. 20 min, an effect which had less latency after the addition of Ca2+. These latter findings argue against degradation and/or desensitization as factors responsible for the transiency in InsP3 response. It is suggested that Ca2+ released by InsP3 is taken up by a part of the endoplasmic reticulum (ER) not sensitive to InsP3. On metabolism of InsP3, Ca2+ recycles to the InsP3-sensitive pool, implying that this pool indeed has a very high affinity for the ion. The presence of functional mitochondria did not interfere with the recycling process. The ER in pancreatic beta-cells is of major importance in buffering Ca2+, but InsP3 only modulates Ca2+ transport for a restricted period of time following immediately upon its formation. Thereafter the non-sensitive part of the ER takes over the continuous regulation of Ca2+ cycling.  相似文献   
3.
Fura-2 loaded pancreatic beta-cells, isolated from obese hyperglycemic mice, were studied with respect to cytoplasmic free Ca2+ concentration ([Ca2+]i), insulin release and efflux of indicator. In the absence of glucose there was a continuous efflux of fura-2, which was markedly increased by stimulation with a high concentration of the sugar. Probenecid both reduced basal efflux of fura-2 and prevented that promoted by glucose. There was no interference of the drug with glucose-induced either insulin release or rise in [Ca2+]i. When applying fura-2 in pancreatic beta-cells, the use of probenecid markedly improves the measurements of [Ca2+]i.  相似文献   
4.
The derivatisation of intact rat hepatocytes with monobromobimane resulted in rapid labelling of accessible protein thiols in several subcellular fractions. The derivatisation procedure did not cause acute cytotoxicity, nor did it alter the buoyant densities of the fractions or their gross protein compositions. Quantitation of the fluorescence irreversibly associated with the fractions demonstrated considerable intracellular heterogeneity in this pool of thiols. Values were highest in cytosol (ca. 90 nmol/mg protein), intermediate in microsomes (ca. 65 nmol/mg protein) and mitochondria (ca. 45 nmol/mg protein) and lowest in a crude fraction containing both nuclei and plasma membrane (ca. 35 nmol/mg protein). Similar values were obtained from microsomes and cytosol derivatised after fractionation but there were significant increases of ca. 100% in corresponding values from isolated mitochondria and the nuclear/plasma membrane fraction. These results are discussed in terms of the dynamic fluxes in monobromobimane protein thiols during fractionation and the applicability of this noninvasive method to studies of the mechanism(s) of toxicity of reactive xenobiotics and the role(s) of protein thiols in normal cellular function.  相似文献   
5.
Influence of basal glucose concentration on the response evoked by subsequent stimulation with the sugar, was evaluated by investigating changes in free cytoplasmic Ca2+ concentration, [Ca2+]i, and insulin release, using beta-cells isolated from obese hyperglycemic mice. When increasing the glucose concentration from 0 to either 11 or 20 mM, there was a transient decrease in both [Ca2+]i and insulin release. The decrease was followed by a pronounced increase in both of the parameters. When increasing the basal glucose concentration, the initial decrease gradually disappeared, being abolished already at 5 mM of the sugar and the subsequent increase appeared more rapidly. It is suggested that the observed decrease in [Ca2+]i and thereby insulin release reflects a phenomenon associated with fuel deprived beta-cells.  相似文献   
6.
The transport of Cd2+ and the effects of this ion on secretory activity and metabolism were investigated in beta cell-rich pancreatic islets isolated from obese-hyperglycemic mice. The endogenous cadmium content was 2.5 mumol/kg dry wt. After 60 min of incubation in a Ca2+-deficient medium containing 2.5 microM Cd2+ the islet cadmium content increased to 0.18 mmol/kg dry wt. This uptake was reduced by approx. 50% in the presence of 1.28 mM Ca2+. The incorporation of Cd2+ was stimulated either by raising the concentration of glucose to 20 mM or K+ to 30.9 mM. Whereas D-600 suppressed the stimulatory effect of glucose by 75%, it completely abolished that obtained with high K+. Only about 40% of the incorporated cadmium was mobilized during 60 min of incubation in a Cd2+-free medium containing 0.5 mM EGTA. It was possible to demonstrate a glucose-induced suppression of Cd2+ efflux into a Ca2+-deficient medium. Concentrations of Cd2+ up to 2.5 microM did not affect glucose oxidation, whereas, there was a progressive inhibition when the Cd2+ concentration was above 10 microM. Basal insulin release was stimulated by 5 microM Cd2+. At a concentration of 160 microM, Cd2+ did not affect basal insulin release but significantly inhibited the secretory response to glucose. It is concluded that the beta cell uptake of Cd2+ is facilitated by the activation of voltage-dependent Ca2+ channels. Apparently, the accumulation of Cd2+ mimics that of Ca2+ also involving a component of intracellular sequestration promoted by glucose.  相似文献   
7.
The effects of 12-O-tetradecanoylphorbol 13-acetate (TPA) on the handling of Ca2+ and insulin release were investigated in the clonal insulin-producing cell line RINm5F. The presence of the phorbol ester lowered the free cytoplasmic Ca2+ and suppressed the increase obtained by depolarization with high concentrations of K+. Despite the lowering in cytoplasmic Ca2+ by TPA, there was a concomitant stimulation of insulin release indicating that one feature of protein kinase C activation is to make the secretory system more sensitive to Ca2+. Furthermore, there was no interaction of TPA with the mechanisms responsible for inositol 1,4,5-tris(phosphate) induced Ca2+ release or Ca2+ uptake in permeabilized cells. Although TPA slightly depolarized the RINm5F cells there was no interference with K+-induced depolarization. It is suggested that an additional effect of protein kinase C activation in these cells, is to stimulate the extrusion of Ca2+ over the plasma membrane.  相似文献   
8.
The effects of the combinations of leaf rust inoculation at different growth stages and initial inoculum levels on leaf rust development and yield of winter wheat cultivars, McNair 1003 and Coker 762 were evaluated. Disease onset stage and initial inoculum level affected the rate of leaf rust development and shape of the disease progress curves in both cultivars. Epidemics with common onset stages and different initial inoculum levels differed in area under the disease progress curve (AUDPC). Leaf rust epidemics initiated at Feeke's growth stages 5, 7, and 10 reduced yield in both cultivars. Leaf rust epidemics initiated early with high inoculum levels had the greatest deleterious effect on yield. Maximum losses due to leaf rust were 30–40 %. Yield loss was directly related to AUDPC when the AUDPC varied from 500 to 1700 in McNair 1003 and from 250 to 1700 in Coker 762. Yield reduction was mainly due to reduction in grain weight.  相似文献   
9.
10.
We examined population substructure of bottlenose dolphins ( Tursiops sp). in Shark Bay, Western Australia, using 10 highly polymorphic microsatellite loci, and mitochondrial DNA (mtDNA). For microsatellite analysis, 302 different animals were sampled from seven localities throughout the bay. Analysis of genetic differentiation between sampling localities showed a significant correlation between the number of migrants ( Nm ) calculated from F ST, R ST and private alleles, and distance between localities–a pattern of isolation-by-distance. For mtDNA, 220 individuals from all seven localities were sequenced for a 351 base pair fragment of the control region, resulting in eight haplotypes, with two distinct clusters of haplotypes. Values of F ST and (φ)ST for mtDNA yielded statistically significant differences, mostly between localities that were not adjacent to each other, suggesting female gene flow over a scale larger than the sampled localities. We also observed a significant correlation between the number of female migrants calculated from F ST and φST and the distance of sampling localities. Our results indicate that dispersal in female dolphins in Shark Bay is more restricted than that of males.  相似文献   
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