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41.
Nitrosomethyl-n-butylamine and its derivatives, labeled withdeuterium in the methyl group or at the alpha position of thebutyl group, were given to rats in drinking water at equimolardoses for approximately 20 weeks. Two concentrations were used,16 mg/l and 6.25 mg/1. The unlabeled compound was not as toxicas its analog labeled in the methyl group, which caused theearly death of some of the test animals. The methyl-labeledcompound was a more effective carcinogen, and the butyl-labeledcompound was a less effective carcinogen, than the unlabeledcompound, as measured by the rate of death of animals with tumorsof the esophagus. Almost all of the surviving animals died withesophageal tumors, basal cell papillomas and carcinomas. 相似文献
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Nitrosopiperidine and three derivatives substituted in the 4-positionwere fed to female F 344 rats in drinking water at equimolarconcentration. The substituents were phenyl, cyclohexyl andtertiary-butyl. Like nitrosopiperidine, the t-butyl- and phenyl-derivativesinduced tumors of the upper gastrointestinal tract (esophagus,forestomach and tongue), but the animals given nitrosopiperidinedied earlier and after a smaller total dose. The rats given4-phenylnitrosopiperidine also had a high incidence of tumorsof the liver, both hepatocellular carcinomas and angiosarcomas.These tumors were absent from untreated animals of this strain.In contrast, no induced tumors were observed in rats treatedwith 4-cyclohexylnitrosopiperidine. 相似文献
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Disruption of a PEX1–PEX6 interaction is the most common cause of the neurologic disorders Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease 下载免费PDF全文
Brian V. Geisbrecht Cynthia S. Collins Bernadette E. Reuber Stephen J. Gould 《Proceedings of the National Academy of Sciences of the United States of America》1998,95(15):8630-8635
Peroxisomal matrix protein import requires the action of two AAA ATPases, PEX1 and PEX6. Mutations in either the PEX1 or PEX6 gene are the most common cause of the lethal neurologic disorders Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease and account for disease in 80% of all such patients. We report here that overexpression of PEX6 can suppress the phenotypes of certain PEX1-deficient cells, that overexpression of PEX1 can suppress the phenotypes of certain PEX6-deficient cells, and that these instances of suppression are allele-specific and require partial activity of the mutated gene. In addition to genetic evidence for interaction between PEX1 and PEX6, we find that the PEX1 and PEX6 proteins interact in the yeast two-hybrid assay and physically associate with one another in vitro. We previously identified a missense mutation in PEX1, G843D, which attenuates PEX1 function and is the most common cause of these diseases, present in one-third of all such patients. The G843D mutation attenuates the interaction between PEX1 and PEX6 in both the two-hybrid system and in vitro and appears to be suppressed by overexpression of PEX6. We conclude that PEX1 and PEX6 form a complex of central importance to peroxisome biogenesis and that mutations affecting this complex constitute the most common cause of the Zellweger syndrome spectrum of diseases. 相似文献
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Reuber M 《Epilepsy & behavior : E&B》2008,12(4):622-635
Psychogenic nonepileptic seizures (PNES) superficially resemble epileptic seizures, but are not associated with ictal electrical discharges in the brain. PNES constitute one of the most important differential diagnoses of epilepsy. However, despite the fact they have been recognized as a distinctive clinical phenomenon for centuries and that access to video/EEG monitoring has allowed clinicians to make near-certain diagnoses for several decades, our understanding of the etiology, underlying mental processes, and, subsequently, subdifferentiation, nosology, and treatment remains seriously deficient. Emphasizing the clinical picture throughout, the first part of this article is intended to "look and look again" at what we know about the epidemiology, semiology, clinical context, treatment, and prognosis of PNES. The second part is dedicated to the questions that remain to be answered. It argues that the most important reason our understanding of PNES remains limited is the focus on the visible manifestations of PNES or the seizures themselves. In contrast, subjective seizure manifestations and the biographic or clinical context in which they occur have been relatively neglected. 相似文献
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Melvin D. Reuber MD 《Archives of environmental & occupational health》2013,68(5):792-797
Inbred Buffalo strain 4-, 8-, 12-, 24-, and 52- week-old male and female rats were given a choline-deficient diet for 22 weeks. Cirrhosis of the liver varied from mild to severe. The incidence and severity of the cirrhosis was comparable for males and females 4 weeks of age at the start of the experiment. The incidence in males and females 8, 12, and 24 weeks of age was similar, but the severity of the cirrhosis was greater in the males. Both the incidence and the degree of cirrhosis in the 52-week-old females were remarkably less than in males of the same age or in younger females. Survival time in male and female rats 4 weeks of age, male rats 8 weeks of age, and males and females 52 weeks of age at the beginning of the choline-deficient diet was less than in animals of other ages. 相似文献
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Melvin D. Reuber M.D Bethesda Md 《Archives of environmental & occupational health》2013,68(6):734-739
Inbred adult Buffalo strain male and female rats were given 0.033% 3-methylcholanthrene continuously in the diet. They were killed after 4, 8, 12, 16, 24, and 52 weeks. The incidence of rats with thyroiditis tended to increase with continued ingestion of the chemical. The lesion was observed earlier in the female than in male rats, and the incidence increased faster with time on the diet. The most striking finding was the severe thyroiditis (as compared with mild or moderate thyroiditis) in most animals, regardless of when they were killed. It is concluded that the lesion develops “suddenly” rather than progressing from mild to moderate, then severe thyroiditis. 相似文献