全文获取类型
收费全文 | 2004篇 |
免费 | 117篇 |
国内免费 | 11篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 71篇 |
妇产科学 | 47篇 |
基础医学 | 334篇 |
口腔科学 | 14篇 |
临床医学 | 252篇 |
内科学 | 457篇 |
皮肤病学 | 39篇 |
神经病学 | 260篇 |
特种医学 | 23篇 |
外科学 | 161篇 |
综合类 | 7篇 |
预防医学 | 143篇 |
眼科学 | 17篇 |
药学 | 171篇 |
中国医学 | 3篇 |
肿瘤学 | 130篇 |
出版年
2023年 | 12篇 |
2022年 | 19篇 |
2021年 | 41篇 |
2020年 | 19篇 |
2019年 | 43篇 |
2018年 | 46篇 |
2017年 | 43篇 |
2016年 | 44篇 |
2015年 | 36篇 |
2014年 | 75篇 |
2013年 | 100篇 |
2012年 | 153篇 |
2011年 | 154篇 |
2010年 | 72篇 |
2009年 | 103篇 |
2008年 | 147篇 |
2007年 | 160篇 |
2006年 | 154篇 |
2005年 | 163篇 |
2004年 | 147篇 |
2003年 | 114篇 |
2002年 | 100篇 |
2001年 | 9篇 |
2000年 | 13篇 |
1999年 | 12篇 |
1998年 | 18篇 |
1997年 | 18篇 |
1996年 | 12篇 |
1995年 | 13篇 |
1994年 | 18篇 |
1993年 | 10篇 |
1992年 | 12篇 |
1991年 | 6篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1988年 | 13篇 |
1987年 | 6篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1983年 | 5篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1977年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有2132条查询结果,搜索用时 15 毫秒
41.
Fatini C Gensini F Sticchi E Battaglini B Angotti C Conforti ML Generini S Pignone A Abbate R Matucci-Cerinic M 《The American journal of medicine》2002,112(7):540-544
PURPOSE: Systemic sclerosis is characterized by progressive microvascular occlusion and fibrosis and by an imbalance in the fibrinolytic system. In vivo and in vitro studies suggest that the renin-angiotensin system partly regulates vascular fibrinolytic balance. Angiotensin II increases the production and secretion of plasminogen activator inhibitor-1, while angiotensin-converting enzyme (ACE) contributes to reduced production of tissue plasminogen activator and endothelial nitric oxide synthesis by bradykinin degradation. The aim of our study was to investigate the effects of ACE insertion/deletion (I/D) and endothelial nitric oxide synthase (eNOS) Glu298Asp (G894-->T) and T-786-->C polymorphisms in patients with systemic sclerosis. SUBJECTS AND METHODS: We studied 73 consecutive patients (47 with limited and 26 with diffuse cutaneous systemic sclerosis) and 112 control subjects. ACE I/D and eNOS polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The ACE I/D and the eNOS G894-->T polymorphisms were more common in patients than in controls (for the ACE D allele: odds ratio [OR] = 3.4; 95% confidence interval [CI]: 1.5 to 7.9; P = 0.003; for the eNOS T allele: OR = 1.9; 95% CI: 1.0 to 3.4; P = 0.04). There was no association between the eNOS T-786-->C polymorphism and systemic sclerosis. CONCLUSIONS: Our findings of an increased risk of systemic sclerosis in ACE D and eNOS 894T allele carriers suggest that these polymorphisms may contribute to the pathogenesis of the disease. 相似文献
42.
43.
44.
45.
Frequency of O6‐methylguanine‐DNA methyltransferase promoter methylation in cytological samples from small cell lung cancer
下载免费PDF全文
![点击此处可从《Diagnostic cytopathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Umberto Miglio Ph.D Rosanna Mezzapelle Ph.D Alessia Paganotti B.Sc. Claudia Veggiani B.Sc. Francesca Mercalli M.D. Giuseppe Mancuso M.Sc. Erica Gaudino M.D. Ottavio Rena Ph.D Roberta Buosi M.D. Renzo Boldorini M.D. 《Diagnostic cytopathology》2015,43(11):947-952
Background. In a phase II study for patients with relapsed small cell lung cancer (SCLC), the administration of Temozolomide, an alkylating agent used in gliomas and anaplastic astrocytoma, showed a effective activity when O6‐methylguanine‐DNA methyltransferase (MGMT) gene promoter was methylated. Methods. We tested the feasibility of MGMT promoter status evaluation in small biopsies and cytological specimens routinely processed for diagnostic purposes. We tested samples from 56 patients with SCLC: 30 tissue biopsies, 17 fine‐needle aspiration biopsy, 8 bronchial washing, and 1 was a sputum. Biopsies and fine‐needle aspiration biopsy were fixed in formalin, bronchial washing and sputum in Dubosq Brazil. DNA was extracted after macrodissection of the areas containing the maximum number of cancer cells. MGMT promoter methylation status was assessed by methylation specific PCR. Results. Methylation analysis was obtained in 54 samples (54/56) and failed in two bronchial wash. MGMT promoter was methylated in 35.2% of the cases without any significant difference between histological and cytological samples (37.9% vs. 32%). Conclusion. MGMT promoter methylation is present in SCLC and cytological samples are perfectly adequate for methylation analysis, even if they were taken during routine diagnostic procedures, using different fixative and with low number and percentage of cancer cells. Diagn. Cytopathol. 2015;43:947–952. © 2015 Wiley Periodicals, Inc. 相似文献
46.
47.
Opt-out HIV screening is recommended by the CDC for patients in all healthcare settings. We examined correlates of HIV testing refusal among urban emergency department (ED) patients. Confidential free HIV screening was offered to 32,633 ED patients in an urban tertiary care facility in Washington, DC, during May 2007–December 2011. Demographic differences in testing refusals were examined using χ2 tests and generalized linear models. HIV testing refusal rates were 47.7 % 95 % CI (46.7–48.7), 11.7 % (11.0–12.4), 10.7 % (10.0–11.4), 16.9 % (15.9–17.9) and 26.9 % (25.6–28.2) in 2007, 2008, 2009, 2010 and 2011 respectively. Persons 33–54 years of age [adjusted prevalence ratio (APR) 1.42, (1.36–1.48)] and those ≥55 years [APR 1.39 (1.31–1.47)], versus 33–54 years; and females versus males [APR 1.07 (1.02–1.11)] were more likely to refuse testing. Opt-out HIV testing is feasible and sustainable in urban ED settings. Efforts are needed to encourage testing among older patients and women. 相似文献
48.
Stefano Marastoni Eva Andreuzzi Alice Paulitti Roberta Colladel Rosanna Pellicani Federico Todaro Alvise Schiavinato Paolo Bonaldo Alfonso Colombatti Maurizio Mongiat 《The Journal of pathology》2014,232(4):391-404
EMILIN2 is an extracellular matrix (ECM) protein that exerts contradictory effects within the tumour microenvironment: it induces apoptosis in a number of tumour cells, but it also enhances tumour neo‐angiogenesis. In this study, we describe a new mechanism by which EMILIN2 attenuates tumour cell viability. Based on sequence homology with the cysteine‐rich domain (CRD) of the Frizzled receptors, we hypothesized that EMILIN2 could affect Wnt signalling activation and demonstrate direct interaction with the Wnt1 ligand. This physical binding leads to decreased LRP6 phosphorylation and to the down‐modulation of β‐catenin, TAZ and their target genes. As a consequence, EMILIN2 negatively affects the viability, migration and tumourigenic potential of MDA‐MB‐231 breast cancer cells in a number of two‐ and three‐dimensional in vitro assays. EMILIN2 does not modulate Wnt signalling downstream of the Wnt–Frizzled interaction, since it does not affect the activation of the pathway following treatment with the GSK3 inhibitors LiCl and CHIR99021. The interaction with Wnt1 and the subsequent biological effects require the presence of the EMI domain, as there is no effect with a deletion mutant lacking this domain. Moreover, in vivo experiments show that the ectopic expression of EMILIN2, as well as treatment with the recombinant protein, significantly reduce tumour growth and dissemination of cancer cells in nude mice. Accordingly, the tumour samples are characterized by a significant down‐regulation of the Wnt signalling pathway. Altogether, these findings provide further evidence of the complex regulations governed by EMILIN2 in the tumour microenvironment, and they identify a key extracellular regulator of the Wnt signalling pathway. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
49.
Rosanna Piccirillo Fabio Demontis Norbert Perrimon Alfred L. Goldberg 《Developmental dynamics》2014,243(2):201-215
Background: The loss of skeletal muscle mass (atrophy) that accompanies disuse and systemic diseases is highly debilitating. Although the pathogenesis of this condition has been primarily studied in mammals, Drosophila is emerging as an attractive system to investigate some of the mechanisms involved in muscle growth and atrophy. Results: In this review, we highlight the outstanding unsolved questions that may benefit from a combination of studies in both flies and mammals. In particular, we discuss how different environmental stimuli and signaling pathways influence muscle mass and strength and how a variety of disease states can cause muscle wasting. Conclusions: Studies in Drosophila and mammals should help identify molecular targets for the treatment of muscle wasting in humans. Developmental Dynamics 243:201–215, 2014. © 2013 Wiley Periodicals, Inc. 相似文献
50.
A CGG‐Repeat Expansion Mutation in ZNF713 Causes FRA7A: Association with Autistic Spectrum Disorder in Two Families
下载免费PDF全文
![点击此处可从《Human mutation》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Sofie Metsu Jacqueline K. Rainger Kim Debacker Birgitta Bernhard Liesbeth Rooms Daria Grafodatskaya Rosanna Weksberg Eric Fombonne Martin S. Taylor Stephen W. Scherer R. Frank Kooy David R. FitzPatrick 《Human mutation》2014,35(11):1295-1300
We report de novo occurrence of the 7p11.2 folate‐sensitive fragile site FRA7A in a male with an autistic spectrum disorder (ASD) due to a CGG‐repeat expansion mutation (~450 repeats) in a 5′ intron of ZNF713. This expanded allele showed hypermethylation of the adjacent CpG island with reduced ZNF713 expression observed in a proband‐derived lymphoblastoid cell line (LCL). His unaffected mother carried an unmethylated premutation (85 repeats). This CGG‐repeat showed length polymorphism in control samples (five to 22 repeats). In a second unrelated family, three siblings with ASD and their unaffected father were found to carry FRA7A premutations, which were partially or mosaically methylated. In one of the affected siblings, mitotic instability of the premutation was observed. ZNF713 expression in LCLs in this family was increased in three of these four premutation carriers. A firm link cannot yet be established between ASD and the repeat expansion mutation but plausible pathogenic mechanisms are discussed. 相似文献