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Biochemical mechanisms of cephaloridine nephrotoxicity 总被引:1,自引:0,他引:1
R S Goldstein P F Smith J B Tarloff L Contardi G F Rush J B Hook 《Life sciences》1988,42(19):1809-1816
Large doses of the cephalosporin antibiotic, cephaloridine, produce acute proximal tubular necrosis in humans and in laboratory animals. Cephaloridine is actively transported into the proximal tubular cell by an organic anion transport system while transport across the lumenal membrane into tubular fluid appears restricted. High intracellular concentrations of cephaloridine are attained in the proximal tubular cell which are critical to the development of nephrotoxicity. There is substantial evidence indicating that oxidative stress plays a major role in cephaloridine nephrotoxicity. Cephaloridine depletes reduced glutathione, increases oxidized glutathione and induces lipid peroxidation in renal cortical tissue. The molecular mechanisms mediating cephaloridine-induced oxidative stress are not well understood. Inhibition in gluconeogenesis is a relatively early biochemical effect of cephaloridine and is independent of lipid peroxidation. Furthermore, cephaloridine inhibits gluconeogenesis in both target (kidney) and non-target (liver) organs of cephaloridine toxicity. Since glucose is not a major fuel of proximal tubular cells, it is unlikely that cephaloridine-induced tubular necrosis is mediated by the effects of this drug on glucose synthesis. 相似文献
3.
The serine carboxylesterase from horse serum was characterized by amino acid composition, peptide mapping, molecular and subunit weights, and sequencing of the amino acids around the essential serine residue at the active site. A protocol was developed for using reversed-phase high-performance liquid chromatography as the final step to obtain homogeneous preparations of horse serum carboxylesterase. Amounts sufficient for determining the amino acid composition and for peptide maps were obtained from a partially purified starting material which contained approximately 55% carboxylesterase. The amino acid composition, like the subunit weight (70,800 +/- 1400), was similar to the corresponding values reported for other serine carboxylesterases. However, the amino acid sequence of the tryptic digest fragment containing the essential nucleophilic seryl residue differed significantly from the corresponding sequences of other mammalian serine carboxylesterases. 相似文献
4.
Previous studies have demonstrated that various cell types can produce and secrete polyornithine-attachable neurite promoting factors when cultured. This study describes an endogenous source of polyornithine-attachable neurite promoting factors. The active material extracted from an avian smooth muscle, the expansor secundariorum, is able to enhance neurite outgrowth from embryonic chick sympathetic neurons when applied to a polyornithine substrate. Unlike other polyornithine attachable factors, the material is also able to support the neurons for at least 72 hr in the absence of any added survival factors. Partial purification of the active material was achieved by affinity chromatography on polyornithine-Sepharose. The findings support the proposal that neurite promoting factors may have a definite physiological role in addition to their well established in vitro activity. 相似文献
5.
The experiments were designed to detect somatopetal transport of [14C]noradrenaline in the postganglionic sympathetic nerves supplying the cat spleen and sheep eye. The animals were treated with nialamide to protect the radioactive noradrenaline, after uptake into the nerve terminals, from monoamine oxidase. In the spleen, the transmitter stores were labelled by infusion of [14C]noradrenaline into a branch of the splenic artery. The branches of the nerves to the infused and non-infused sides of the spleen were ligated in an attempt to arrest, distal to the constriction, any noradrenaline transported somatopetally in the axons from their terminals. After 24 hr, however, there was less radioactivity in the nerves distal compared to proximal to the constriction, despite heavier labelling of the terminal transmitter stores in the infused portion of the spleen. The proximal accumulation of radioactivity could be attributed to a somatofugal transport of [14C]noradrenaline. Experiments were also done on the intact sympathetic nerve supply of the sheep eye. The sympathetic nerve terminals in the smooth muscle of the left eye were heavily labelled 5 days after the injection of [14C]noradrenaline into the left vitreous humour. However, both superior cervical ganglia were only lightly labelled, and there was no significant difference in the radioactivity present in the two ganglia. The results provide no support for a bidirectional transport of noradrenaline in sympathetic nerves but are consistent with a somatofugal transport of the amine storage vesicles from their site of synthesis in the soma to the axon terminals. 相似文献
6.
Circular deoxyribonucleic acid was isolated from Shigella dysenteriae Y6R and was found to consist of six species having molecular weights of 10(6), 1.3 x 10(6), 2.6 x 10(6), 3.8 x 10(6), 20 x 10(6), and 24 x 10(6) daltons. These size classes were partially resolved by sucrose density gradient centrifugation. The minicircles (10(6) and 1.3 x 10(6)) were found to have a buoyant density in CsCl of 1.710 g/ml. The 3.8 x 10(6) dalton class had a density of 1.707 g/ml. The two largest species had a density of 1.702 g/ml. Two other strains, S. sonnei II and S. dysenteriae 60, also contained circular deoxyribonucleic acid. 相似文献
7.
The relationship between the source strength and the “manifest vector” in the Einthoven Triangle is derived for a line and
a point dipole source and confirmed experimentally. The result permits the interpretation of the standard ECG leads in absolute
terms and corrected for body size. The manifest vector is shown to be approximately
times what it would be in an otherwise similar circular slab which circumscribes the triangle. 相似文献
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Induction of a 'stress' protein in intact mammalian organs after the intravenous administration of sodium arsenite 总被引:4,自引:0,他引:4
The profile of nascent proteins synthesized in various rabbit organs after the intravenous injection of sodium arsenite was analyzed by the cell-free translation of purified polysomes. Examination of the translation products of polysomes isolated 1 hr after injection of sodium arsenite revealed a marked induction of synthesis of a protein of molecular weight 74,000 (74K) in the kidney, heart and liver which was similar to a 'heat shock' protein which was induced in these organs after elevation of body temperature by 2.5 to 3 degrees C. Synthesis of the 74K protein was not detected in the translation products of brain polysomes isolated 1 hr after sodium arsenite injection. 相似文献