全文获取类型
收费全文 | 336篇 |
免费 | 13篇 |
国内免费 | 12篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 8篇 |
妇产科学 | 6篇 |
基础医学 | 32篇 |
口腔科学 | 8篇 |
临床医学 | 29篇 |
内科学 | 73篇 |
皮肤病学 | 6篇 |
神经病学 | 11篇 |
特种医学 | 81篇 |
外科学 | 36篇 |
综合类 | 9篇 |
预防医学 | 12篇 |
眼科学 | 7篇 |
药学 | 29篇 |
肿瘤学 | 13篇 |
出版年
2022年 | 5篇 |
2021年 | 6篇 |
2020年 | 1篇 |
2019年 | 8篇 |
2018年 | 10篇 |
2017年 | 1篇 |
2016年 | 7篇 |
2015年 | 6篇 |
2014年 | 8篇 |
2013年 | 11篇 |
2012年 | 15篇 |
2011年 | 8篇 |
2010年 | 12篇 |
2009年 | 12篇 |
2008年 | 12篇 |
2007年 | 14篇 |
2006年 | 8篇 |
2005年 | 6篇 |
2004年 | 14篇 |
2003年 | 9篇 |
2002年 | 9篇 |
2001年 | 3篇 |
2000年 | 7篇 |
1999年 | 9篇 |
1998年 | 10篇 |
1997年 | 12篇 |
1996年 | 9篇 |
1995年 | 9篇 |
1994年 | 11篇 |
1993年 | 13篇 |
1992年 | 3篇 |
1991年 | 4篇 |
1990年 | 4篇 |
1989年 | 8篇 |
1988年 | 8篇 |
1987年 | 10篇 |
1986年 | 10篇 |
1985年 | 6篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 9篇 |
1977年 | 10篇 |
1976年 | 3篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1963年 | 1篇 |
排序方式: 共有361条查询结果,搜索用时 91 毫秒
41.
Jun-Xiao Zhang Lei Fu Richarda M de Voer Marc-Manuel Hahn Peng Jin Chen-Xi Lv Eugène TP Verwiel Marjolijn JL Ligtenberg Nicoline Hoogerbrugge Roland P Kuiper Jian-Qiu Sheng Ad Geurts van Kessel 《World journal of gastroenterology : WJG》2015,21(14):4136-4149
AIM: To investigate whether whole-exome sequencing may serve as an efficient method to identify known or novel colorectal cancer(CRC) predisposing genes in early-onset or familial CRC cases.METHODS: We performed whole-exome sequencing in 23 Chinese patients from 21 families with nonpolyposis CRC diagnosed at ≤ 40 years of age, or from multiple affected CRC families with at least 1 firstdegree relative diagnosed with CRC at ≤ 55 years of age.Genomic DNA from blood was enriched for exome sequences using the Sure Select Human All Exon Kit, version 2(Agilent Technologies) and sequencing was performed on an Illumina Hi Seq 2000 platform.Data were processed through an analytical pipeline to search for rare germline variants in known or novel CRC predisposing genes.RESULTS: In total, 32 germline variants in 23 genes were identified and confirmed by Sanger sequencing.In 6 of the 21 families(29%), we identified 7 mutations in 3 known CRC predisposing genes including MLH1(5 patients), MSH2(1 patient), and MUTYH(biallelic, 1 patient), five of which were reported as pathogenic.Inthe remaining 15 families, we identified 20 rare and novel potentially deleterious variants in 19 genes, six of which were truncating mutations.One previously unreported variant identified in a conserved region of EIF2AK4(p.Glu738_Asp739insA rgA rg) was found to represent a local Chinese variant, which was significantly enriched in our early-onset CRC patient cohort compared to a control cohort of 100 healthy Chinese individuals scored negative by colonoscopy(33.3% vs 7%, P 0.001).CONCLUSION: Whole-exome sequencing of early-onset or familial CRC cases serves as an efficient method to identify known and potential pathogenic variants in established and novel candidate CRC predisposing genes. 相似文献
42.
Induction of NK activity in large granular lymphocyte leukemia: activation with anti-CD3 monoclonal antibody and interleukin 2 总被引:4,自引:0,他引:4
Large granular lymphocyte (LGL) leukemia is a rare disease characterized by clonal expansion of LGL associated with chronic neutropenia, multiple auto-antibodies, and occasionally polyarthritis. We studied cell surface antigen expression and functional activity of leukemic LGL from ten such patients. Using two-color flow cytometric analysis, we found that leukemic LGL from all ten patients expressed the CD3 and HNK-1 markers, while cells from only four patients expressed IgG Fc receptors (FcR). The LGL leukemic cells had little or no NK activity (defined as MHC-nonrestricted cytotoxicity against K562 target cells); however, NK activity could be induced in leukemic LGL by in vitro treatment with as little as 0.05 microgram/mL of anti-CD3 monoclonal antibody. Cell sorting experiments demonstrated that NK activity was induced in CD3+ leukemic LGL (either CD3+, HNK-1+ or CD3+, FcR+) with anti-CD3 monoclonal antibody but not in normal CD3+, FcR- T cells. Treatment with purified interleukin 2 (IL 2) also caused direct activation of some CD3+ leukemic LGL. Despite induction with anti-CD3 MAb or IL 2, activated leukemic LGL did not proliferate or express high density IL 2 receptors detectable by cell sorter analysis. Treatment with alpha interferon had minimal effect on NK activity of LGL leukemic cells. These results suggest that leukemic LGL may provide a useful model for examining the signals required for LGL maturation and activation. 相似文献
43.
CD3+ large granular lymphocyte (LGL) leukemia is a disease of unknown etiology characterized by clonal proliferation of T cells that usually express T-cell receptor (TCR) alpha beta heterodimers. The purpose of this study was to identify the variable (V), joining (J), and diversity (D) region TCR beta-chain genes expressed by CD3+ LGL leukemic cells in an attempt to gain insights into the etiology of this disorder. Twelve patients with LGL leukemia were studied, including seven with both LGL leukemia and rheumatoid arthritis (RA). RA is also a disease of unknown etiology that occurs frequently in patients with LGL leukemia. Clonally expanded T cells that express specific TCR V beta genes have been identified in fluid and tissue specimens from the joints of patients with RA. In this study, V beta expression was determined by PCR using a panel of 22 unique V beta primers to amplify cDNA prepared from peripheral blood mononuclear cells (PBMC). A dominant V beta gene product was readily apparent in all patients. To confirm that the dominant V beta gene originated from a clonal expansion, DNA fragments corresponding to the dominant V beta genes were subcloned into plasmids and independently isolated recombinants were sequenced. V-D-J region sequences that occurred repeatedly indicated clonality. The V beta and J beta genes expressed by the leukemic cells showed a pattern of distribution that followed the frequency with which these genes are represented in the peripheral blood. The residues corresponding to the third complementarity-determining region of the TCR beta chain were different in all cases. A specific pattern of VDJ usage was not identified for those patients with both LGL leukemia and RA; however, utilization of V beta-6 by LGL clones (N = 3) was observed only in the setting of RA. These data suggest that leukemic CD3+ LGL cells have been clonally transformed in a random fashion with respect to the TCR beta chain. 相似文献
44.
This study examined the effects of cyclical etidronate, when used in
routine clinical practice, on the prevention of fracture. Information was
obtained from 550 general practices in the UK that provide their medical
records to the General Practice Research Database. A total of 7977 patients
taking cyclical etidronate treatment and 7977 age-, sex- and
practice-matched control patients with a diagnosis of osteoporosis were
analysed. People taking cyclical etidronate had a significantly reduced
risk of non-vertebral fracture (by 20%) and of hip fracture (by 34%)
relative to the osteoporosis control patients. The relative risk of
non-vertebral fracture was 0.80 (95% confidence interval 0.70-0.92), that
of hip fracture 0.66 (0.51-0.85) and that of wrist fracture 0.81
(0.58-1.14). When fracture incidence rates were compared between the two
groups, the rate of non-vertebral, hip and wrist fracture decreased
significantly (P < 0.05) with increasing etidronate exposure. The
results of this study complement and extend clinical observations
supporting the anti-fracture efficacy of cyclical etidronate therapy.
相似文献
45.
46.
47.
以Fura-2/AM为细胞内钙离子的荧光指示剂,用AR-CM-MIC阳离子测定系统,直接测定了体外培养的新生大鼠神经细胞内游离钙([Ca2+]i)值,并观察了小檗碱(Ber)的影响。结果表明,Ber对神经细胞静息[Ca2+]i无明显影响,Ber1~100μmol·L-1能剂量依赖地抑制去甲肾上腺素和H2O2引起的[Ca2+]i升高,其IC50分别为39.9和17.9μmol·L-1。高剂量Ber(10~100μmol·L-1)能抑制高K+引起的[Ca2+]i升高。姐果提示,Ber对去甲肾上腺素,高K+及H2O2引起的[Ca2+]i升高的抑制作用可能是其抗脑缺血作用机制之一。 相似文献
48.
Temporomandibular joint arthrography has been helpful in selecting patients for reconstructive surgery who have severe temporomandibular joint dysfunction. Structural abnormalities of the soft tissues can be demonstrated where only minimal osseous changes are seen on tomography. The normal arthrographic anatomy of the joint is reviewed and normal and pathological joints are illustrated. 相似文献
49.
The pathogenesis of peripheral aneurysms of the central nervous system: a subject review from the AFIP 总被引:1,自引:0,他引:1
Most central nervous system aneurysms occur around the circle of Willis, and are congenital or arteriosclerotic in origin when in that location. Peripherally located aneurysms are either idiopathic or secondary to infection, tumor embolus (from choriocarcinoma and cardiac myxoma), Moyamoya disease, or trauma. The pathophysiologic features of these aneurysms are discussed. 相似文献
50.