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排序方式: 共有4525条查询结果,搜索用时 312 毫秒
61.
Danny D. Shen James P. Hosler Richard L. Schroder Daniel L. Azarnoff 《Journal of pharmacokinetics and pharmacodynamics》1980,8(1):53-68
The pharmacokinetics of hydralazine (H) and its acid-labile hydrazone metabolites were compared in rapid and slow acetylators. Following a 20-mg intravenous infusion, the elimination half-life (t1/2) and the apparent volume of distribution of H did not differ between the two groups. Plasma clearance estimates approached hepatic blood flow. When a single 100-mg dose of H was given-orally, the area under the plasma concentration-time curve (AUC) and systemic availability () in slow acetylators were, on the average, twice as high as in the rapid acetylators, indicating a difference in the extent of first-pass metabolism of the drug. Furthermore, the observed in the slow individuals exceeded theoretical predictions. Hence saturation of first-pass metabolism of H is suggested, and a nonlinear relationship between AUC and oral dose of H was indeed observed in the three subjects studied with two doses. The half-life of decline of the acidlabile metabolites was similar to the t1/2 of H. The AUCs for metabolites were 4–12 times larger than for the parentdrug. However, the ratio between the metabolite AUC and drug AUC did not differ irrespective ofroutes of administration or the acetylator status.This study was supported in part by Grant RR 828 from United States Public Health Service and a Research Starter grant from the Pharmaceutical Manufacturers Association Foundation, Inc. (D. D. S.). 相似文献
62.
Summary Five and 10 mg single oral doses of a new vasodilator antihypertensive, endralazine (E) were given on separate occasions to 17 normal male volunteers (8 slow, 7 heterozygous fast and 2 homozygous fast acetylators). The homozygous fast acetylators were excluded from statistical comparisons. Only small differences were observed in the pharmacokinetics of E between the phenotypes and there was no evidence of non-linearity at the 2 dose levels studied. Terminal half-lives ranged from 2.59 to 7.14 h with a mean of 4.30±1.08 h for the 5 mg dose and 4.25±1.09 h for the 10 mg dose. There was no significant difference in half-lives between slow and heterozygous fast acetylators. The mean area under the plasma level-time curve (AUC
0
) was 18.2% lower (p<0.05) in the heterozygous fast acetylators than in the slow acetylators following the 5 mg dose and 11.0% lower (p>0.05) following the 10 mg dose. Extremely rapid absorption of the drug precluded accurate estimation of absorption rates. The AUC
0
of the acetylation metabolite (methyltriazoloendralazine) was small compared to that of E although higher in the heterozygous fast acetylators than in the slow acetylators (p<0.01). 相似文献
63.
肺癌患者外周血T淋巴细胞亚群变化及其临床意义 总被引:1,自引:0,他引:1
[目的]检测肺癌患者T淋巴细胞亚群变化.[方法]采用SAP法检测42例肺癌患者及20例正常对照组的外周血T淋巴细胞亚群,并将肺癌中转移组和未转移组分别与正常对照组进行比较.[结果](1)肺癌转移组CD3 、CD 4阳性率低于未转移组(P<0.05),CD 4/CD 8比值比正常组及未转移组低(P<0.05).(2)未转移组CD 8低于正常组及转移组(P<0.05).[结论]肺癌患者细胞免疫功能低下,并且细胞免疫功能随病情进展逐步受到抑制. 相似文献
64.
E. Fombonne P. Bolton J. Prior H. Jordan M. Rutter 《Journal of child psychology and psychiatry, and allied disciplines》1997,38(6):667-683
First-degree relatives of 99 autism probands and of 36 Down's syndrome controls were assessed with standardised tests of intellectual functioning, reading, and spelling. Higher mean verbal IQ scores, and discrepancies in favour of verbal scores, were characteristic of autism relatives. No consistent differences were found on performance scales, reading, and spelling tests. Among autism relatives, siblings affected with the broad phenotype of autism had significantly lower IQ scores and poorer reading and spelling performances than unaffected siblings. However, the small size of the cognitive difference and the lack of a distinctive cognitive profile indicates that standardised cognitive measures used in this study are unlikely to improve the operationalised definition of the broad phenotype of autism. The slightly superior verbal performance of relatives in the autism group might represent some form of heterozygote advantage. 相似文献
65.
Phenotypic shift in human differentiated gastric cancers from gastric to intestinal epithelial cell type during disease progression 总被引:3,自引:1,他引:3
Akemi Yoshikawa Ken-ichi Inada Takasuke Yamachika Nobuyuki Shimizu Michio Kaminishi Masae Tatematsu 《Gastric cancer》1998,1(2):134-141
Background. The phenotypic expression of tumor cells is widely thought to resemble that of the tissue of origin. In the present study,
to assess phenotypic changes that occur with disease progression, we investigated human differentiated gastric cancers at
different depths of invasion for component cancer cell types.
Methods. Using a combined mucin histochemical and immunohistochemical approach, we classified surgical specimens of 301 differentiated
gastric cancers into three types: gastric epithelial cell (G) type, intestinal epithelial cell (I) type and mixed gastric
and intestinal (GI) type, according to the phenotypic differentiation of the component cancer cells. The relation between
the phenotypic type of cancer and their depth of invasion was evaluated.
Results. The proportion of G type cancers was 41.4% in early (tumor invasion of mucosa or submucosa) cases, decreasing to 22.2% in
advanced (tumor invasion of muscularis propia or deeper) cases, whereas the proportion of I type cancers increased with progressive
disease from 23.5% to 31.1% (P < 0.01). Cancers invading the subserosa or deeper included more I type cases and fewer G type than cancers limited to the
mucosa (P < 0.01). In most cases of each phenotypic type, intestinal metaplasia was recognized in the surrounding background mucosa,
but no clear relation was shown between the phenotype of cancers and the degree of intestinal metaplasia in the background
mucosa, suggesting that intestinal metaplasia is not always a preneoplastic lesion.
Conclusions. A phenotypic shift from G to I type expression was observed with the progression of human differentiated gastric cancers.
Intestinalization may occur independently in cancerous and noncancerous gastric mucosa.
Received for publication on May 1, 1998; accepted on Oct. 22, 1998 相似文献
66.
细胞色素氧化酶CYP3A4基因突变与表型研究进展 总被引:1,自引:0,他引:1
细胞色素P4503A4在许多内源性及外源性化合物的氧化及还原代谢中起关键作用,对CYP3A4基因表达的研究具有重要意义。本文对CYP3A4基因突变及其表型特征加以总结。 相似文献
67.
Rice JP Hartz SM Agrawal A Almasy L Bennett S Breslau N Bucholz KK Doheny KF Edenberg HJ Goate AM Hesselbrock V Howells WB Johnson EO Kramer J Krueger RF Kuperman S Laurie C Manolio TA Neuman RJ Nurnberger JI Porjesz B Pugh E Ramos EM Saccone N Saccone S Schuckit M Bierut LJ;the GENEVA Consortium 《Addiction (Abingdon, England)》2012,107(11):2019-2028
AIMS: Nicotine dependence is a highly heritable disorder associated with severe medical morbidity and mortality. Recent meta-analyses have found novel genetic loci associated with cigarettes per day (CPD), a proxy for nicotine dependence. The aim of this paper is to evaluate the importance of phenotype definition (i.e. CPD versus Fagerstr?m Test for Cigarette Dependence (FTCD) score as a measure of nicotine dependence) on genome-wide association studies of nicotine dependence. DESIGN: Genome-wide association study. SETTING: Community sample. PARTICIPANTS: A total of 3365 subjects who had smoked at least one cigarette were selected from the Study of Addiction: Genetics and Environment (SAGE). Of the participants, 2267 were European Americans, 999 were African Americans. MEASUREMENTS: Nicotine dependence defined by FTCD score ≥4, CPD. FINDINGS: The genetic locus most strongly associated with nicotine dependence was rs1451240 on chromosome 8 in the region of CHRNB3 [odds ratio (OR)?=?0.65, P?=?2.4?×?10(-8) ]. This association was further strengthened in a meta-analysis with a previously published data set (combined P?=?6.7?×?10(-16) , total n?=?4200). When CPD was used as an alternate phenotype, the association no longer reached genome-wide significance (β?=?-0.08, P?=?0.0004). CONCLUSIONS: Daily cigarette consumption and the Fagerstrom Test for Cigarette Dependence show different associations with polymorphisms in genetic loci. 相似文献
68.
69.
Willem M.A. Verhoeven Jos I.M. Egger Luc Goffin Laura J.C.M. van Zutven Grazia M.S. Mancini 《European journal of medical genetics》2013,56(6):331-335
A female patient, 20 years of age, is reported with a history characterized by developmental and psychomotor delay, and during grammar-school period increasing learning problems, ritualistic behaviours and social withdrawal. Subsequently, challenging and autistic-like behaviours became prominent. The patient showed mild facial dysmorphisms, long thin fingers with bilateral mild short V metacarpals, and hyperlaxity of the joints. Neuropsychiatric examination disclosed obsessive, ritualistic behaviours and vague ideas of reference. Neuropsychological assessment demonstrated mild intellectual disability, mental inflexibility and incongruent affect. MRI-scanning of the brain showed no relevant abnormalities. Genome wide SNP array analysis revealed a 1.2 Mb de novo interstitial microdeletion in 4q25 comprising 11 genes, that was considered to be causative for the developmental delay, perseverative cognitive phenotype and dysmorphisms.To the authors knowledge, this is the first report of a de novo 4q25 microdeletion that presents with a specific behavioural phenotype. 相似文献
70.