全文获取类型
收费全文 | 36349篇 |
免费 | 1729篇 |
国内免费 | 295篇 |
专业分类
耳鼻咽喉 | 309篇 |
儿科学 | 655篇 |
妇产科学 | 414篇 |
基础医学 | 4816篇 |
口腔科学 | 1024篇 |
临床医学 | 2124篇 |
内科学 | 8996篇 |
皮肤病学 | 855篇 |
神经病学 | 2516篇 |
特种医学 | 1258篇 |
外科学 | 6474篇 |
综合类 | 149篇 |
一般理论 | 1篇 |
预防医学 | 1032篇 |
眼科学 | 654篇 |
药学 | 2183篇 |
中国医学 | 125篇 |
肿瘤学 | 4788篇 |
出版年
2024年 | 25篇 |
2023年 | 204篇 |
2022年 | 539篇 |
2021年 | 883篇 |
2020年 | 451篇 |
2019年 | 654篇 |
2018年 | 853篇 |
2017年 | 664篇 |
2016年 | 777篇 |
2015年 | 805篇 |
2014年 | 1084篇 |
2013年 | 1392篇 |
2012年 | 2244篇 |
2011年 | 2620篇 |
2010年 | 1479篇 |
2009年 | 1217篇 |
2008年 | 2244篇 |
2007年 | 2486篇 |
2006年 | 2324篇 |
2005年 | 2500篇 |
2004年 | 2414篇 |
2003年 | 2411篇 |
2002年 | 2416篇 |
2001年 | 378篇 |
2000年 | 315篇 |
1999年 | 442篇 |
1998年 | 586篇 |
1997年 | 463篇 |
1996年 | 434篇 |
1995年 | 371篇 |
1994年 | 327篇 |
1993年 | 299篇 |
1992年 | 219篇 |
1991年 | 195篇 |
1990年 | 196篇 |
1989年 | 182篇 |
1988年 | 165篇 |
1987年 | 122篇 |
1986年 | 111篇 |
1985年 | 97篇 |
1984年 | 112篇 |
1983年 | 91篇 |
1982年 | 72篇 |
1981年 | 88篇 |
1980年 | 84篇 |
1979年 | 66篇 |
1978年 | 42篇 |
1977年 | 29篇 |
1976年 | 25篇 |
1975年 | 25篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
992.
993.
994.
Go Kuwata Terumi Kamisawa Koichi Koizumi Taku Tabata Seiichi Hara Sawako Kuruma Takashi Fujiwara Kazuro Chiba Hideto Egashira Junko Fujiwara Takeo Arakawa Kumiko Momma Shinichiro Horiguchi 《Gut and liver》2014,8(1):29-34
Background/Aims
Ulcerative colitis (UC) is sometimes associated with autoimmune pancreatitis (AIP). Infiltration of immunoglobulin G4 (IgG4)-positive plasma cells is sometimes detected in the colonic mucosa of AIP or UC patients. This study aimed to clarify the relation between UC and IgG4.Methods
Associations with UC were reviewed in 85 AIP patients. IgG4 immunostaining was performed on biopsy specimens from the colonic mucosa of 14 AIP and 32 UC patients.Results
UC was confirmed in two cases (type 1 AIP, n=1; suspected type 2 AIP, n=1). Abundant infiltration of IgG4-positive plasma cells in the colonic mucosa was detected in the case of suspected type 2 AIP with UC and two cases of type 1 AIP without colitis. Abundant infiltration of IgG4-positive plasma cells was detected in 10 UC cases (IgG4-present, 31%). Although 72% of IgG4-absent UC patients showed mild disease activity, 70% of IgG4-present patients showed moderate to severe disease activity (p<0.05).Conclusions
UC is sometimes associated with AIP, but it seems that UC is not a manifestation of IgG4-related disease. Infiltration of IgG4-positive plasma cells is sometimes detectable in the colonic mucosa of UC patients and is associated with disease activity. 相似文献995.
Autoantibodies to RuvBL1 and RuvBL2: A Novel Systemic Sclerosis–Related Antibody Associated With Diffuse Cutaneous and Skeletal Muscle Involvement
下载免费PDF全文
![点击此处可从《Arthritis care & research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
996.
Simin Lu Kohsuke Kanekura Takashi Hara Jana Mahadevan Larry D. Spears Christine M. Oslowski Rita Martinez Mayu Yamazaki-Inoue Masashi Toyoda Amber Neilson Patrick Blanner Cris M. Brown Clay F. Semenkovich Bess A. Marshall Tamara Hershey Akihiro Umezawa Peter A. Greer Fumihiko Urano 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(49):E5292-E5301
Wolfram syndrome is a genetic disorder characterized by diabetes and neurodegeneration and considered as an endoplasmic reticulum (ER) disease. Despite the underlying importance of ER dysfunction in Wolfram syndrome and the identification of two causative genes, Wolfram syndrome 1 (WFS1) and Wolfram syndrome 2 (WFS2), a molecular mechanism linking the ER to death of neurons and β cells has not been elucidated. Here we implicate calpain 2 in the mechanism of cell death in Wolfram syndrome. Calpain 2 is negatively regulated by WFS2, and elevated activation of calpain 2 by WFS2-knockdown correlates with cell death. Calpain activation is also induced by high cytosolic calcium mediated by the loss of function of WFS1. Calpain hyperactivation is observed in the WFS1 knockout mouse as well as in neural progenitor cells derived from induced pluripotent stem (iPS) cells of Wolfram syndrome patients. A small-scale small-molecule screen targeting ER calcium homeostasis reveals that dantrolene can prevent cell death in neural progenitor cells derived from Wolfram syndrome iPS cells. Our results demonstrate that calpain and the pathway leading its activation provides potential therapeutic targets for Wolfram syndrome and other ER diseases.The endoplasmic reticulum (ER) takes center stage for protein production, redox regulation, calcium homeostasis, and cell death (1, 2). It follows that genetic or acquired ER dysfunction can trigger a variety of common diseases, including neurodegenerative diseases, metabolic disorders, and inflammatory bowel disease (3, 4). Breakdown in ER function is also associated with genetic disorders such as Wolfram syndrome (5–8). It is challenging to determine the exact effects of ER dysfunction on the fate of affected cells in common diseases with polygenic and multifactorial etiologies. In contrast, we reasoned that it should be possible to define the role of ER dysfunction in mechanistically homogenous patient populations, especially in rare diseases with a monogenic basis, such as Wolfram syndrome (9).Wolfram syndrome (OMIM 222300) is a rare autosomal recessive disorder characterized by juvenile-onset diabetes mellitus and bilateral optic atrophy (7). Insulin-dependent diabetes usually occurs as the initial manifestation during the first decade of life, whereas the diagnosis of Wolfram syndrome is invariably later, with onset of symptoms in the second and ensuing decades (7, 10, 11). Two causative genes for this genetic disorder have been identified and named Wolfram syndrome 1 (WFS1) and Wolfram syndrome 2 (WFS2) (12, 13). It has been shown that multiple mutations in the WFS1 gene, as well as a specific mutation in the WFS2 gene, lead to β cell death and neurodegeneration through ER and mitochondrial dysfunction (5, 6, 14–16). WFS1 gene variants are also associated with a risk of type 2 diabetes (17). Moreover, a specific WFS1 variant can cause autosomal dominant diabetes (18), raising the possibility that this rare disorder is relevant to common molecular mechanisms altered in diabetes and other human chronic diseases in which ER dysfunction is involved.Despite the underlying importance of ER malfunction in Wolfram syndrome, and the identification of WFS1 and WFS2 genes, a molecular mechanism linking the ER to death of neurons and β cells has not been elucidated. Here we show that the calpain protease provides a mechanistic link between the ER and death of neurons and β cells in Wolfram syndrome. 相似文献
997.
998.
Rheumatoid arthritis (RA) mainly affects various joints of the body, including the temporomandibular joint (TMJ), and it involves an infiltration of autoantibodies and inflammatory leukocytes into articular tissues and the synovium. Initially, the synovial lining tissue becomes engaged with several kinds of infiltrating cells, including osteoclasts, macrophages, lymphocytes, and plasma cells. Eventually, bone degradation occurs. In order to elucidate the best therapy for RA, a comprehensive study of RA pathogenesis needs to be completed. In this article, we discuss a Fas-deficient condition which develops into RA, with an emphasis on the role of sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling which induces the migration of osteoclast precursor cells. We describe that Fas/S1P1 signaling via NF-κB activation in osteoclasts is a key factor in TMJ-RA severity and we discuss a strategy for blocking nuclear translocation of the p50 NF-κB subunit as a potential therapy for attenuating osteoclastogenesis. 相似文献
999.
Akitoshi Kinoshita Hayato Miyachi Hiromichi Matsushita Miharu Yabe Tomohiko Taki Tomoyuki Watanabe Akiko M. Saito Daisuke Tomizawa Takashi Taga Hiroyuki Takahashi Hidemasa Matsuo Kumi Kodama Kentaro Ohki Yasuhide Hayashi Akio Tawa Keizo Horibe Souichi Adachi 《British journal of haematology》2014,167(1):80-86
The clinical characteristics and prognostic relevance of acute myeloid leukaemia (AML) with myelodysplastic features remains to be clarified in children. We prospectively examined 443 newly diagnosed patients in a multicentre clinical trial for paediatric de novo AML, and found ‘AML with myelodysplasia‐related changes’ (AML‐MRC) according to the 2008 World Health Organization classification in 93 (21·0%), in whom 59 were diagnosed from myelodysplasia‐related cytogenetics alone, 28 from multilineage dysplasia alone and six from a combination of both. Compared with 111 patients with ‘AML, not otherwise specified’ (AML‐NOS), patients with ‘AML‐MRC’ presented at a younger age, with a lower white blood cell count, higher incidence of 20–30% bone marrow blasts, unfavourable cytogenetics and a lower frequency of Fms‐like tyrosine kinase 3 internal tandem duplication (FLT3‐ITD), NPM1 and CEBPA mutations. Complete remission rate and 3‐year probability of event‐free survival were significantly worse in ‘AML‐MRC’ patients (67·7 vs. 85·6%, P < 0·01, 37·1% vs. 53·8%, P = 0·02, respectively), but 3‐year overall survival and relapse‐free survival were comparable with ‘AML‐NOS’ patients. By multivariate analysis, FLT3‐ITD was solely associated with worse overall survival. These results support the distinctive features of the category ‘AML‐MRC’ even in children. 相似文献
1000.
Michinori Ogura Kiyoshi Ando Tatsuya Suzuki Kenichi Ishizawa Sung Yong Oh Kuniaki Itoh Kazuhito Yamamoto Wing Yan Au Hwei‐Fang Tien Yoshihiro Matsuno Takashi Terauchi Keiko Yamamoto Masahiko Mori Yoshinobu Tanaka Takashi Shimamoto Kensei Tobinai Won Seog Kim 《British journal of haematology》2014,165(6):768-776
Although initial rituximab‐containing chemotherapies achieve high response rates, indolent B‐cell non‐Hodgkin lymphoma (B‐NHL), such as follicular lymphoma (FL), is still incurable. Therefore, new effective agents with novel mechanisms are anticipated. In this multicentre phase II study, patients with relapsed/refractory indolent B‐NHL and mantle cell lymphoma (MCL) received vorinostat 200 mg twice daily for 14 consecutive days in a 21‐d cycle until disease progression or unacceptable toxicity occurred. The primary endpoint was overall response rate (ORR) in FL patients and safety and tolerability in all patients. Secondary endpoints included progression‐free survival (PFS). Fifty‐six eligible patients were enrolled; 50 patients (39 with FL, seven with other B‐NHL, and four with MCL) were evaluable for ORR, and 40 patients had received rituximab‐containing prior chemotherapeutic regimens. For the 39 patients with FL, the ORR was 49% [95% confidence interval (CI): 32·4, 65·2] and the median PFS was 20 months (95% CI: 11·2, 29·7). Major toxicities were manageable grade 3/4 thrombocytopenia and neutropenia. Vorinostat offers sustained antitumour activity in patients with relapsed or refractory FL with an acceptable safety profile. Further investigation of vorinostat for clinical efficacy is warranted. 相似文献