全文获取类型
收费全文 | 8916篇 |
免费 | 554篇 |
国内免费 | 71篇 |
专业分类
耳鼻咽喉 | 57篇 |
儿科学 | 261篇 |
妇产科学 | 216篇 |
基础医学 | 1354篇 |
口腔科学 | 141篇 |
临床医学 | 667篇 |
内科学 | 2301篇 |
皮肤病学 | 283篇 |
神经病学 | 779篇 |
特种医学 | 324篇 |
外科学 | 934篇 |
综合类 | 17篇 |
预防医学 | 539篇 |
眼科学 | 91篇 |
药学 | 685篇 |
中国医学 | 16篇 |
肿瘤学 | 876篇 |
出版年
2024年 | 7篇 |
2023年 | 68篇 |
2022年 | 139篇 |
2021年 | 295篇 |
2020年 | 166篇 |
2019年 | 238篇 |
2018年 | 249篇 |
2017年 | 193篇 |
2016年 | 249篇 |
2015年 | 285篇 |
2014年 | 344篇 |
2013年 | 447篇 |
2012年 | 713篇 |
2011年 | 734篇 |
2010年 | 374篇 |
2009年 | 353篇 |
2008年 | 584篇 |
2007年 | 564篇 |
2006年 | 571篇 |
2005年 | 584篇 |
2004年 | 510篇 |
2003年 | 462篇 |
2002年 | 386篇 |
2001年 | 93篇 |
2000年 | 86篇 |
1999年 | 101篇 |
1998年 | 88篇 |
1997年 | 67篇 |
1996年 | 61篇 |
1995年 | 48篇 |
1994年 | 39篇 |
1993年 | 37篇 |
1992年 | 49篇 |
1991年 | 45篇 |
1990年 | 38篇 |
1989年 | 31篇 |
1988年 | 26篇 |
1987年 | 22篇 |
1986年 | 29篇 |
1985年 | 21篇 |
1984年 | 15篇 |
1983年 | 13篇 |
1981年 | 9篇 |
1980年 | 9篇 |
1979年 | 13篇 |
1978年 | 9篇 |
1977年 | 10篇 |
1975年 | 8篇 |
1974年 | 8篇 |
1966年 | 8篇 |
排序方式: 共有9541条查询结果,搜索用时 578 毫秒
61.
Tuccillo C Cuomo A Rocco A Martinelli E Staibano S Mascolo M Gravina AG Nardone G Ricci V Ciardiello F Del Vecchio Blanco C Romano M 《The Journal of pathology》2005,207(3):277-284
Host response plays a major role in the pathogenesis of Helicobacter pylori-induced gastroduodenal disease including adenocarcinoma of the distal stomach. Vascular endothelial growth factor (VEGF) is an important modulator of gastric mucosal repair and is overexpressed in gastric cancer. The present study sought to evaluate the expression of VEGF in the gastric mucosa of H. pylori-infected and H. pylori-non-infected dyspeptic patients. Fifteen H. pylori-infected and 15 H. pylori-non-infected dyspeptic patients were studied. Diagnosis of H. pylori infection was based on rapid urease test and histology. VEGF protein expression was assessed by western blotting. VEGF mRNA expression was assessed by RT-PCR. VEGF localization in the gastric mucosa and neo-angiogenesis were determined by immunohistochemistry. VEGF protein and mRNA expression was significantly greater in H. pylori-infected than in non-infected patients. Immunohistochemistry showed that VEGF expression was more intense in the gastric gland compartment of H. pylori-infected mucosa than in the non-infected mucosa. The increase in VEGF expression was associated with a significant increase in neo-angiogenesis as assessed by determination of CD34-positive micro-vessels. H. pylori gastritis is therefore associated with up-regulation of VEGF expression, which parallels the increased formation of blood vessels in the gastric mucosa. It is postulated that increased VEGF expression and neo-angiogenesis may contribute to H. pylori-related gastric carcinogenesis. 相似文献
62.
63.
A proteolipid, capable of inducing hydroxyapatite in vitro, can be isolated from human aortic calcified lesions, noncalcified lesions, and nonlesion tissue obtained at autopsy. Analysis of the amino acid composition after acid hydrolysis showed all nucleators to be high in the hydrophobic amino acids glycine and alanine. Estimation of the molecular weight of the nucleator, extracted from calcified lesions, by gel filtration and lipid content showed a minimum molecular weight of 469,000 Da. All nucleators were characterized by the presence of acidic phospholipids which may have a role in the mechanism of calcification. 相似文献
64.
Mariano Rocchi Angela Covone Giovanni Romeo Raffaella Faraonio Vittorio Colantuoni 《Somatic Cell and Molecular Genetics》1989,15(2):185-190
The human gene coding for RBP4 has been assigned to 10q2324 using a panel of somatic cell hybrids and in situ hybridization experiments. The mapping of the human RBP1, previously assigned by our group to chromosome 3 using a panel of somatic cell hybrids, was restricted to the region 3q2122 using in situ experiments and Southern blots of genomic DNA from a hybrid retaining a portion of chromosome 3.R.F. is recipient of a Research Grant from A.I.R.C. 相似文献
65.
McKay JD Thompson D Lesueur F Stankov K Pastore A Watfah C Strolz S Riccabona G Moncayo R Romeo G Goldgar DE 《Journal of medical genetics》2004,41(6):407-412
Background: Familial non-medullary thyroid cancer (fNMTC) is a complex genetic disorder that is more aggressive than its sporadic counterpart. Thus far, three genetic loci have been implicated in susceptibility to fNMTC by linkage analysis. Methods: We used linkage analysis to test the significance of two of the known susceptibility loci for fNMTC, TCO on 19p13 and NMTC1 on 2q21 in 10 fNMTC families, nine of which present with cell oxyphilia, a rare histological phenotype associated with TCO. Furthermore, we used two-locus linkage analysis to examine the possibility that the TCO and NMTC1 loci interact to increase the risk of NMTC. Results: The 10 families provided evidence for linkage at both TCO and NMTC, with LOD scores of 1.56 and 2.85, respectively. Two-locus linkage analysis, using a multiplicative risk model for the development of NMTC, achieved a maximum LOD of 3.92, with an LOD of 4.51 when assuming 70% of families were linked, indicating that the segregation in these families is consistent with an interaction model. Most of this evidence came from a large Tyrolean family that singularly achieved a two-locus LOD of 3.21. Conclusions: These results provide further evidence that susceptibility genes for fNMTC exist at 19p13 and 2q21, and furthermore, raise the possibility that in a subset of fNMTC pedigrees, these loci interact resulting in significantly increased risk of NMTC for patients that carry both susceptibility loci. 相似文献
66.
Christina Brahe Stefania Zappata Isabella Velon Enrico Bertini Serenella Servidei Pietro Tonali Giovanni Neri 《American journal of medical genetics. Part A》1993,45(3):408-411
Linkage analysis and prenatal prediction in families segregating autosomal recessive spinal muscular atrophy (SMA) has become feasible since the assignment of the locus responsible for type I-III SMA to region 5q12-q13.3. We have performed a segregation study of SMA in Italian families using molecular probes and highly informative PCR-based polymorphic markers. In one family, a 7-year-old boy affected with type III SMA and an 8-year-old apparently healthy brother had identical haplotypes. These findings prompted us to reexamine the apparently unaffected child. His neurological exam was normal. However, the electromyography (EMG) showed a pattern consistent with chronic SMA. To our knowledge this is the first example of presymptomatic diagnosis of SMA based on genotype analysis. © 1993 Wiley-Liss, Inc. 相似文献
67.
Biallelic somatic inactivation of the mismatch repair gene MLH1 in a primary skin melanoma 总被引:2,自引:0,他引:2
Castiglia D Pagani E Alvino E Vernole P Marra G Cannavò E Jiricny J Zambruno G D'Atri S 《Genes, chromosomes & cancer》2003,37(2):165-175
Inactivation of mismatch repair (MMR) genes has been linked to the hereditary nonpolyposis colon cancer syndrome and to a subset of sporadic cancers. A phenotypic characteristic of tumors with defective MMR is microsatellite instability (MSI). Although MSI has been reported in a proportion of cutaneous melanomas, inactivation of MMR genes in this tumor type has not been detected thus far. We recently described a human melanoma cell line, PR-Mel, and a cutaneous metastasis from the same patient, which displayed a MMR defect, and showed high MSI. Here we report that in the PR-Mel cell line both MLH1 alleles are somatically inactivated. One allele is lost through a chromosomal deletion of the region 3p21-24, whereas the remaining allele harbors a G --> A transition at position -1 of the acceptor splice site of intron 15, leading to the in-frame skipping of exon 16. The primary melanoma of the PR patient shows loss of heterozygosity at the BAT21 microsatellite marker, located in the MLH1 gene, and does not express the MLH1 and PMS2 proteins. Moreover, it harbors the same mutation detected in the PR-Mel cells. These results demonstrate that biallelic inactivation of MLH1 had occurred in the primary melanoma of the PR patient and suggest that disruption of MMR might have had a role in the development of the melanoma. This is the first report in which genetic defects leading to disruption of MMR function in a human melanoma have been identified. 相似文献
68.
Dpc4 is expressed in virtually all primary and metastatic pancreatic endocrine carcinomas 总被引:2,自引:0,他引:2
Scarpa A Orlandini S Moore PS Lemoine NR Beghelli S Baron A Falconi M Zamboni G 《Virchows Archiv : an international journal of pathology》2002,440(2):155-159
DPC4/Smad4 is inactivated in about 50% of pancreatic ductal cancers. It has been recently reported that this gene is also inactivated in neoplasms arising from pancreatic islet cells, a phenomenon suggested to be related to similar progressions of malignancy found in common ductal cancers. To evaluate this possibility, we analysed 20 metastases of pancreatic endocrine carcinomas and their corresponding primary lesion for inactivation of DPC4 using immunohistochemical staining. In fact, immunohistochemical labelling has been shown to correlate with DPC4 gene status with high sensitivity and specificity. The cancers included 18 nonfunctioning tumours, one gastrinoma and one ViPoma all with liver, nodal and/or adrenal metastases. Seventeen were well-differentiated and three poorly differentiated endocrine carcinomas. Dpc4 expression was absent in only one primary well-differentiated endocrine cancer and its liver metastasis, while all the remaining 19 primary tumours and their metastases stained positive for the protein. All positively staining cases showed diffuse cytoplasmic and nuclear staining in virtually all neoplastic cells. Our data suggest that DPC4 is only rarely involved in pancreatic endocrine tumourigenesis and give further weight to the hypothesis that tumours arising from pancreatic exocrine and endocrine epithelia are genetically distinct. 相似文献
69.
Fucosidosis revisited: a review of 77 patients 总被引:4,自引:0,他引:4
P J Willems R Gatti J K Darby G Romeo P Durand J E Dumon J S O'Brien 《American journal of medical genetics》1991,38(1):111-131
Fucosidosis is a rare, autosomal recessive, lysosomal storage disorder caused by a severe deficiency of alpha-L-fucosidase in all tissues. We have conducted a review of fucosidosis, compiling data from published reports and an international questionnaire survey. Seventy-seven patients affected with fucosidosis of which 19 had not been reported before have been identified. A major aim of the present study was to define the natural history of fucosidosis. The clinical picture of fucosidosis consists of progressive mental (95%) and motor (87%) deterioration, coarse facies (79%), growth retardation (78%), recurrent infections (78%), dysostosis multiplex (58%), angiokeratoma corporis diffusum (52%), visceromegaly (44%), and seizures (38%). Whereas the original fucosidosis patients described by Durand et al. (J. Pediatr 75:665-674, 1969) were decerebrate and died before age 5 years, most fucosidosis patients have a slower course of degeneration. Mortality before age 5 years was observed in only 7 patients (9%), whereas 36 patients (64%) reached the second decade. We did not find evidence for the existence of clinical heterogeneity with a rapidly progressive type I and a slowly progressive type II fucosidosis as suggested in the literature. Instead, there seems to exist a wide continuous clinical spectrum. At the biochemical level no heterogeneity in residual fucosidase enzyme activity or cross-reacting immunoreactive fucosidase protein was observed. At the DNA level at least 4 different mutations must be responsible for fucosidosis. These genotypic differences however do not explain the observed phenotypic differences. 相似文献
70.
Age and sex influence on oxidative damage and functional status in human skeletal muscle 总被引:3,自引:0,他引:3
Fanò Giorgio Mecocci Patrizia Vecchiet Jacopo Belia Silvia Fulle Stefania Polidori M. Cristina Felzani Giorgio Senin Umberto Vecchiet Leonardo Beal M. Flint 《Journal of muscle research and cell motility》2001,22(4):345-351
A reduction in muscle mass, with consequent decrease in strength and resistance, is commonly observed with advancing age. In this study we measured markers of oxidative damage to DNA, lipids and proteins, some antioxidant enzyme activities as well Ca2+ transport in sarcoplasmic reticulum membranes in muscle biopsies from vastus lateralis of young and elderly healthy subjects of both sexes in order to evaluate the presence of age- and sex- related differences. We found a significant increase in oxidation of DNA and lipids in the elderly group, more evident in males, and a reduction in catalase and glutathione transferase activities. The experiments on Ca2+ transport showed an abnormal functional response of aged muscle after exposure to caffeine, which increases the opening of Ca2+ channels, as well a reduced activity of the Ca2+ pump in elderly males. From these results we conclude that oxidative stress play an important role in muscle aging and that oxidative damage is much more evident in elderly males, suggesting a gender difference maybe related to hormonal factors.This revised version was published online in September 2005 with corrections to the Cover Date. 相似文献