全文获取类型
收费全文 | 155426篇 |
免费 | 14791篇 |
国内免费 | 4513篇 |
专业分类
耳鼻咽喉 | 996篇 |
儿科学 | 2317篇 |
妇产科学 | 1689篇 |
基础医学 | 25964篇 |
口腔科学 | 3736篇 |
临床医学 | 11016篇 |
内科学 | 21247篇 |
皮肤病学 | 2995篇 |
神经病学 | 13743篇 |
特种医学 | 4238篇 |
外国民族医学 | 33篇 |
外科学 | 13013篇 |
综合类 | 18082篇 |
现状与发展 | 18篇 |
预防医学 | 8721篇 |
眼科学 | 1518篇 |
药学 | 24183篇 |
38篇 | |
中国医学 | 6903篇 |
肿瘤学 | 14280篇 |
出版年
2024年 | 244篇 |
2023年 | 2292篇 |
2022年 | 3384篇 |
2021年 | 6447篇 |
2020年 | 5183篇 |
2019年 | 7918篇 |
2018年 | 7316篇 |
2017年 | 6158篇 |
2016年 | 5246篇 |
2015年 | 6263篇 |
2014年 | 9867篇 |
2013年 | 9721篇 |
2012年 | 8439篇 |
2011年 | 9742篇 |
2010年 | 8227篇 |
2009年 | 8778篇 |
2008年 | 7857篇 |
2007年 | 7776篇 |
2006年 | 6795篇 |
2005年 | 5980篇 |
2004年 | 4380篇 |
2003年 | 4075篇 |
2002年 | 3065篇 |
2001年 | 2643篇 |
2000年 | 2235篇 |
1999年 | 1994篇 |
1998年 | 1893篇 |
1997年 | 1780篇 |
1996年 | 1637篇 |
1995年 | 1514篇 |
1994年 | 1366篇 |
1993年 | 1213篇 |
1992年 | 987篇 |
1991年 | 910篇 |
1990年 | 740篇 |
1989年 | 632篇 |
1988年 | 606篇 |
1987年 | 625篇 |
1986年 | 728篇 |
1985年 | 1239篇 |
1984年 | 1273篇 |
1983年 | 905篇 |
1982年 | 930篇 |
1981年 | 799篇 |
1980年 | 720篇 |
1979年 | 561篇 |
1978年 | 353篇 |
1977年 | 309篇 |
1976年 | 307篇 |
1975年 | 209篇 |
排序方式: 共有10000条查询结果,搜索用时 28 毫秒
991.
Joshua K. Meisner Donna M. Martin 《American journal of medical genetics. Part C, Seminars in medical genetics》2020,184(1):81-89
CHARGE syndrome is characterized by a pattern of congenital anomalies (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth, Genital abnormalities, and Ear abnormalities). De novo mutations of chromodomain helicase DNA binding protein 7 (CHD7) are the primary cause of CHARGE syndrome. The clinical phenotype is highly variable including a wide spectrum of congenital heart defects. Here, we review the range of congenital heart defects and the molecular effects of CHD7 on cardiovascular development that lead to an over‐representation of atrioventricular septal, conotruncal, and aortic arch defects in CHARGE syndrome. Further, we review the overlap of cardiovascular and noncardiovascular comorbidities present in CHARGE and their impact on the peri‐operative morbidity and mortality in individuals with CHARGE syndrome. 相似文献
992.
目的:研究eIF3S10在肺癌中的表达及其与化疗反应的关系,探讨其在肺癌预后中的作用。方法:收集在湖南省肿瘤医院治疗的31例支气管纤维镜检肺癌组织和20例肺良性病变组织及10例肺癌边缘正常组织的石蜡组织切片。采用免疫组织化学技术检测eIF3S10蛋白在肺癌组织、肺良性病变组织和正常肺组织中的表达,并分析eIF3S10表达水平与患者化疗敏感性的关系。结果:肺正常组织和肺良性病变组织中eIF3S10阳性率分别为30%和15%,而肺癌组织中eIF3S10的阳性率达61%。eIF3S10表达水平与化疗敏感性存在一定相关性。结论:肺癌组织中有eIF3S10过表达,而肿瘤组织eIF3S10表达过高可能提示患者对化疗反应敏感。 相似文献
993.
Mannose binding lectin and C3 act as recognition molecules for infectious agents in the vagina 总被引:8,自引:0,他引:8
Pellis V De Seta F Crovella S Bossi F Bulla R Guaschino S Radillo O Garred P Tedesco F 《Clinical and experimental immunology》2005,139(1):120-126
In our study we examined the early complement components in patients with bacterial vaginosis (BV), vulvovaginal candidiasis (VVC) and in healthy controls. The levels of C1q, mannose-binding lectin (MBL) and C3 were measured by ELISA in the cervicovaginal lavage (CVL) from gynaecological patients and controls. No significant differences were observed in the levels of these proteins in the three study groups. Immunofluorescence analysis of the clue cells and Candida hyphae from BV and VVC patients for surface-bound complement components showed the presence of C3, while C1q was undetectable. MBL was revealed on clue cells but not on Candida. Binding of MBL to Candida, grown or cytocentrifuged from the CVL of VVC patients, was found to be pH dependent and occurred between pH 4.5 and pH 5.5. In conclusion, we demonstrated that MBL and C3 present in the vaginal cavity act as recognition molecules for infectious agents that colonize the cervicovaginal mucosa. Our finding that MBL, but not C1q, binds to bacteria and fungi in vagina suggests that the lectin and classical pathways of complement activation may play a different role in immune defence in the female genital tract. 相似文献
994.
Y.?Takeda N.?Shiobara A.?R.?Saniabadi M.?Adachi K.?HiraishiEmail author 《Inflammation research》2004,53(7):277-283
Objective:Evolving evidence of anti-inflammatory effects is observed in patients with rheumatoid arthritis or ulcerative colitis following periodic adsorptive granulocyte and monocyte (GM) apheresis with a column containing cellulose acetate (CA) beads as apheresis carriers. This study was undertaken to obtain insights into mechanisms of anti-inflammatory actions of adsorptive GM apheresis with CA beads.
Methods:In a series of in-vitro experiments, we investigated the effects of plasma proteins and the leucocytes 2 integrin (CD18) on granulocyte adsorption to CA beads.
Results:Granulocyte adsorption to CA beads required plasma IgG, the complement C3 and was inhibited by an antibody to leucocytes CD18. Further, hepatocyte growth factor (HGF) and interleukin-1 receptor antagonist (IL-1ra) which have strong anti-inflammatory actions were released by granulocytes that adhered to CA beads.
Conclusions:Plasma IgG, C3 derived complement activation fragments and leucocytes CD18 are involved in granulocyte adhesion to CA beads and hence the release of HGF and IL-1ra.Received 27 October 2003; returned for revision 16 December 2003; accepted by M. J. Parnham 8 January 2004 相似文献
995.
Early-onset gastric carcinomas display molecular characteristics distinct from gastric carcinomas occurring at a later age 总被引:5,自引:0,他引:5
Carvalho R Milne AN van Rees BP Caspers E Cirnes L Figueiredo C Offerhaus GJ Weterman MA 《The Journal of pathology》2004,204(1):75-83
Gastric cancer is thought to result from a combination of environmental factors and accumulation of specific genetic alterations, and consequently mainly affects older patients (>50 years of age). Fewer than 10% of patients present with the disease before 45 years of age and these young patients are thought to develop carcinomas with a different molecular genetic profile from that of sporadic carcinomas occurring at a later age. Forty early-onset gastric carcinoma resection specimens were characterized for microsatellite instability (MSI) and loss of heterozygosity status using 22 polymorphic microsatellite markers. Twenty-four biopsies were additionally evaluated for the presence of MSI. No MSI was observed in any of the cases analysed. Losses were infrequent, but were most common for the D1S234 (26.1%) and D1S1676 (17.4%) markers, flanking the RUNX3 gene; for the p53ALU (23.1%) and TP53 (15.4%) markers, near the TP53 gene; and for the D16S2624 (17.2%) marker, near the E-cadherin (CDH1) gene. All cases with loss of CDH1, as well as 6/7 cases with loss of TP53, displayed aberrant staining of the corresponding proteins, pointing to a functional role for these proteins in early-onset gastric carcinogenesis. No germline CDH1, TP53 or RUNX3 mutations were detected in any of the cases analysed. No correlation was observed between non-functional E-cadherin and the histological type of the tumours analysed. Finally, Epstein-Barr virus was not detected in any of the cases analysed. On the basis of these results, early-onset gastric carcinomas appear to have characteristics distinct from gastric carcinomas occurring at a later age. 相似文献
996.
Caspase—3与肝细胞癌的细胞凋亡 总被引:3,自引:0,他引:3
Caspase 3是哺乳动物细胞凋亡的关键蛋白酶 ,亦参与了肝细胞癌的细胞凋亡的病理过程。免疫组化分析肝细胞癌中Caspase 3表达强度明显减弱 ,认为在肝细胞癌的发生过程中 ,Caspase 3的活性通过多种途径受到抑制。研究Caspase 3与影响肝细胞癌细胞凋亡各因素之间的关系 ,有助于寻找和开辟肿瘤治疗的新途径。 相似文献
997.
Distal Proctocolitis and n-3 Polyunsaturated Fatty Acids (n-3 PUFAs): The Mucosal Effect In Situ 总被引:1,自引:0,他引:1
Almallah YZ Ewen SW El-Tahir A Mowat NA Brunt PW Sinclair TS Heys SD Eremin O 《Journal of clinical immunology》2000,20(1):68-76
It has been postulated that patients with ulcerative colitis (UC) have altered reactivity of gut-associated lymphoid tissue. In such cases there is intense infiltration of the mucosa with immune competent cells and associated tissue damage. We have shown previously that the dietary supplementation with the n-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) results in significant systemic immune suppression. The aim of this study, therefore, was to evaluate the in situ effect of n-3 PUFAs on distal proctocolitis. Each patient received either fish oil extract (EPA 3.2 g, DHA 2.4 g) (n = 9) or sunflower oil (n = 9) daily in a double blind manner for six months. Monthly assessment included: (1) disease activity using clinical, sigmoidoscopic, and histological scores and (2) immunohistochemical analysis (immunoglobulins, CD profiles) of rectal biopsy specimens (before and after six months supplementation) using monoclonal antibodies and quantitative computer-assisted video image analysis. Prior to receiving supplementation, patients with proctocolitis (n = 18) showed significantly higher numbers of cells expressing CD3 (pan T cells) and HLA-DR and IgM containing cells compared with non-colitic controls (n = 8). Six months supplementation with n-3 PUFAs resulted in significant reduction in the number of cells expressing CD3 and HLA and the percentage of cells containing IgM. There was no significant change in the CD20 nor the percentage of IgG or IgA containing cells in either group of patients with procto-colitis. In patients receiving n-3 PUFA supplementation, there was improvement in the disease activity and histological scores, compared with pretreatment evaluation. This study has demonstrated both evidence of suppression of in situ immune reactivity and concurrent reduction in disease activity in patients with proctocolitis receiving n-3 PUFA supplementation. This may have important implication for therapy in patients with ulcerative colitis. 相似文献
998.
Aims : To determine their significance, we examined the expression pattern of the four epidermal growth factor receptor (EGFR) family members as well as the phosphotyrosine kinase activity in breast tumour tissues.
Fifty-three malignant breast tumours, four breast cancer cell lines, and 10 benign breast tumours were investigated. Fifty-three per cent (28/53) of the malignant tumours expressed EGFR protein, and the majority of these positive tumours were strongly positive. Eighty per cent (8/10) of the benign tumours also expressed EGFR protein, but all in a lower or moderate level. An association between EGFR expression and increasing malignancy grade was found in the group of infiltrating ductal carcinomas. Of the malignant tumours, 35.8% (19/53) expressed c-erbB-2 protein and 17% (9/53) c-erbB-3 protein, while no expression of c-erbB-2 and c-erbB-3 proteins was found in the benign tumours. Contrary to previous reports, we observed c-erbB-4 receptor protein to be less expressed in the malignant breast tumours. The 'normal' breast epithelial cells adjacent to the malignant tumours and the benign tumours demonstrated intensified membrane staining for c-erbB-4, while a number of the malignant tumours demonstrated a weak cytoplasmic staining or were negative. However, several malignant tumours with strong membrane staining for the c-erbB-4 protein were also found. No simple association between the expression of the four receptors and phosphotyrosine kinase activity was found.
Our study has revealed a complex expression pattern of the EGFR family members in breast tumour cells. While the data about EGFR, c-erbB-2, c-erbB-3 and phosphotyrosine are largely in line with what has been reported, we found the c-erbB-4 protein expression to be decreased in the malignant tumours. 相似文献
Methods and results
Fifty-three malignant breast tumours, four breast cancer cell lines, and 10 benign breast tumours were investigated. Fifty-three per cent (28/53) of the malignant tumours expressed EGFR protein, and the majority of these positive tumours were strongly positive. Eighty per cent (8/10) of the benign tumours also expressed EGFR protein, but all in a lower or moderate level. An association between EGFR expression and increasing malignancy grade was found in the group of infiltrating ductal carcinomas. Of the malignant tumours, 35.8% (19/53) expressed c-erbB-2 protein and 17% (9/53) c-erbB-3 protein, while no expression of c-erbB-2 and c-erbB-3 proteins was found in the benign tumours. Contrary to previous reports, we observed c-erbB-4 receptor protein to be less expressed in the malignant breast tumours. The 'normal' breast epithelial cells adjacent to the malignant tumours and the benign tumours demonstrated intensified membrane staining for c-erbB-4, while a number of the malignant tumours demonstrated a weak cytoplasmic staining or were negative. However, several malignant tumours with strong membrane staining for the c-erbB-4 protein were also found. No simple association between the expression of the four receptors and phosphotyrosine kinase activity was found.
Conclusion
Our study has revealed a complex expression pattern of the EGFR family members in breast tumour cells. While the data about EGFR, c-erbB-2, c-erbB-3 and phosphotyrosine are largely in line with what has been reported, we found the c-erbB-4 protein expression to be decreased in the malignant tumours. 相似文献
999.
1000.
Frauke Behrens Uwe Claussen Leslie M. Iyer Eric D. Green Bernhard Horsthemke Robert Williamson Clare Huxley Charles Coutelle 《Chromosome research》1997,5(4):215-220
Centromeres remain the least characterized regions of human chromosomes because they have a very high content of repetitive DNA. Here, we describe a micro-dissection library from the centromeric region of human chromosome 7 and its use for generating sequence tagged sites (STSs). The library contains about 1500 clones with an average insert size of 150 bp and only about 15% of the clones harbour repetitive human DNA. Seven clones hybridizing to alphoid DNA were found to correspond to a fragment of the D7Z2 alphoid array on chromosome 7, thus confirming the origin of the library. A number of clones not containing known repetitive DNA were used to generate STSs that identified yeast artificial chromosomes (YACs) and in turn allowed the STSs to be placed on the physical map. One STS is located between the two Genethon genetic markers closest to the centromere on the q side. Another STS was located 3–4 cM away in 7q11.2, while a third identified YACs containing both low-copy and alphoid sequences that are not yet mapped but are clearly centromeric. The library therefore comprises a collection of sequences from the centromeric region of chromosome 7 that can be used to generate STSs and to map the entire centromeric region.This revised version was published online in November 2005 with corrections to the Cover Date. 相似文献