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81.
Alpha-cyclodextrin glucosyltransferase (alpha-CGTase, EC 2.4.1.19) is an amylolytic enzyme used for the production of alpha-cyclodextrin (alpha-CD), a novel, soluble dietary fiber, from food-grade starch. The safety of an alpha-CGTase preparation obtained by batch fermentation from a recombinant strain of Escherichia coli K12 harboring the alpha-CGTase gene from Klebsiella oxytoca strain M5a1 was examined. In a 13-week subchronic toxicity study in rats, the administration by gavage of the alpha-CGTase preparation at levels of up to 20 ml/kg bw/day, corresponding to a total organic solids dosage of 260 mg/kg bw/day, did not cause any systemic toxic effect. Some signs of irritation were observed in the respiratory tract which occurred, however, in one sex only and/or were not dose-related. Accordingly, these changes were considered to be an unspecific consequence of the reflux and aspiration of the dosing solution. There was no evidence of a genotoxic activity in Ames tests and a chromosome aberration test in cultured human lymphocytes. It is concluded that the examined alpha-CGTase preparation is safe when used for the production of alpha-CD. 相似文献
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Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin 总被引:8,自引:0,他引:8
Wang DS Jonker JW Kato Y Kusuhara H Schinkel AH Sugiyama Y 《The Journal of pharmacology and experimental therapeutics》2002,302(2):510-515
Metformin, a biguanide, is widely used as an oral hypoglycemic agent for the treatment of type 2 diabetes mellitus. The purpose of the present study was to investigate the role of organic cation transporter 1 (Oct1) in the disposition of metformin. Transfection of rat Oct1 cDNA results in the time-dependent and saturable uptake of metformin by the Chinese hamster ovary cell line with K(m) and V(max) values of 377 microM and 1386 pmol/min/mg of protein, respectively. Buformin and phenformin, two other biguanides, were also transported by rOct1 with a higher affinity than metformin: their K(m) values were 49 and 16 microM, respectively. To investigate the role of Oct1 in the disposition of metformin, the tissue distribution of metformin was determined in Oct1 gene-knockout mice after i.v. administration. Distribution of metformin to the liver in Oct1(-/-) mice was more than 30 times lower than that in Oct1(+/+) mice, and can be accounted for by the extracellular space. Distribution to the small intestine was also decreased in Oct1(-/-) mice, whereas that to the kidney as well as the urinary excretion profile showed only minimal differences. In conclusion, the present findings suggest that Oct1 is responsible for the hepatic uptake as well as playing a role in the intestinal uptake of metformin, whereas the renal distribution and excretion are mainly governed by other transport mechanism(s). 相似文献
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85.
The association between depressive symptoms and cognitive decline in community-dwelling elderly persons 总被引:1,自引:0,他引:1
Comijs HC Jonker C Beekman AT Deeg DJ 《International journal of geriatric psychiatry》2001,16(4):361-367
OBJECTIVE: To investigate whether depressive symptoms predict specific types of cognitive decline in order to elucidate the association between late life depression and cognitive decline. BACKGROUND: Mechanisms underlying the association between late life depression and cognitive decline are still unclear. METHOD: Six hundred and forty-one elderly persons of the Longitudinal Aging Study Amsterdam (LASA) aged 70-85 were examined by means of two measurement occasions over a period of 3 years. Depressive symptoms were assessed by means of the CES-D. Various cognitive functions were examined using neuropsychological tests. RESULTS: Depressive symptoms were associated with decline in speed of information processing over a 3-year period, whereas there was no association between depression and increasing memory impairment or global mental deterioration. CONCLUSION: These findings suggest that depressive symptoms are associated with subcortical pathology, most probable white matter lesions. 相似文献
86.
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Cefalu WT; Wagner JD; Bell-Farrow AD; Edwards IJ; Terry JG; Weindruch R; Kemnitz JW 《Toxicological sciences》1999,52(2):49-55
Caloric restriction (CR) has been observed to retard aging processes and
extend the maximum life span in rodents. In an effort to evaluate the
effect of this nutritional intervention on physiologic variables in higher
species, several nonhuman primate trials are ongoing. In particular, a
study evaluating the independent effect of CR on the extent of
atherosclerosis was initiated in 1993 in 32 adult cynomolgus monkeys.
Therefore, the trial was designed to achieve identical cholesterol intake
after animals were randomized to a control group or a calorie-restricted
group (30% reduction from baseline caloric intake). The animals were
routinely evaluated for glycated proteins, plasma insulin and glucose
levels, insulin sensitivity, and specific measures for abdominal fat
distribution by CT scans over a 4-year interval. The results from 4 years
of intervention demonstrate that CR improves cardiovascular risk factors
(such as visceral fat accumulation) and improves insulin sensitivity. In
contrast to other primate studies with normolipidemic animals, CR had no
independent effects on plasma lipid levels and composition in the presence
of equivalent amounts of dietary cholesterol intake. Preliminary analysis
of atherosclerotic lesion extent in the abdominal aorta has failed to
demonstrate differences between control animals and CR animals. Follow- up
studies are being conducted to determine the effect of CR on
atherosclerosis extent in coronary and carotid arteries.
相似文献
88.
89.
JV Leonard JW Seakins K Bartlett J Hyde J Wilson B Clayton 《Archives of disease in childhood》1981,56(1):53-59
The clinical course of 4 patients who had reduced activities of 3-methylcrotonyl CoA carboxylase (also called 3-methylcrotonylglycinuria) is described. Two children presented with a metabolic acidosis, one in the neonatal period and the other with episodes of acidosis that started in the second year of life. In the other 2 children neurological symptoms were prominent, one having infantile spasms and the other developmental regression with a skin rash and alopecia. Three of the children responded well to oral biotin and dietary protein restriction but the fourth, despite a biochemical response to biotin, has a severe neurological handicap. The clinical presentation of inborn errors of 3-methylcrotonyl CoA carboxylase is variable. Metabolic acidosis may not be conspicuous and instead neurological features may predominate. 相似文献
90.
The distinction between true and suspected poisoning in children has not been made clear in previous work on childhood poisoning. A study of suspected poisoning in children under 15 years of age in a defined population of North East Bristol from November 1970 to July 1973 carried out by the Health Education Council Medical Research Division included 53,000 child-years at risk. The number of suspected poisonings was 3-4/1000 population aged under 15 years per year, with a higher incidence in younger age groups. Detailed investigation of the circumstances of the accidents carried out by a multidisciplinary team showed that at least 65%, and possibly as many as 78% were poisoning scares and not true poisoning. The evidence used by the casualty doctor and by the parents to diagnose poisoning was explored, and in many cases was circumstantial. Children with fathers in nonmanual occupations were over-represented. This may reflect differences in patterns of utilization behaviour rather than true differences in incidence. 相似文献