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51.
Ikuko Haruta Etsuko Hashimoto Ikuko Haruta Etsuko Hashimoto Noriyuki Shibata Ikuko Haruta 《Autoimmunity》2013,46(5):372-379
Background: Chronic colitis-harboring TCRα? / ? × AIM? / ? mice showed PBC-like bile duct damage in the liver. Bacterial infection is one of the candidates for the pathogenesis of PBC. We demonstrated that the bacterial cell wall component lipotheicoic acid (LTA) was detected at sites of inflammation around damaged bile ducts in PBC patients. The aim of this study was to investigate the pathophysiology of the liver and other organs in TCRα? / ? × AIM? / ? mice.Methods: Thirteen female TCRα? / ? × AIM? / ? mice were sacrificed at 24 weeks of age. The liver, stomach, small intestine, colon, pancreas, kidney and spleen were studied for pathological examination. Using anti-LTA antibody as the primary antibody, an immunohistochemical study was carried out.Results: In the liver, LTA was mainly detected in the portal area with inflammation, and some of the cytoplasm of hepatocytes. Inflammations were also observed in the stomach, intestine, pancreas and kidney. Throughout the gastrointestinal tract, from the stomach to the colon, LTA was detected in the epithelium at sites of inflammation. Furthermore, LTA was detected around both pancreatic ducts with inflammation and distal renal tubules with inflammation.Conclusions: The development of inflammations in the liver as well as extensive organs, strongly suggests a close relationship between bile duct damage and systemic multifocal epithelial inflammations, perhaps involving bacterial LTA, in TCRα? / ? × AIM? / ? mice. 相似文献
52.
Ikuko Haruta Etsuko Hashimoto Ikuko Haruta Etsuko Hashimoto Yoichiro Kato Ikuko Haruta 《Autoimmunity》2013,46(2):129-135
Aim: Intrahepatic bile ducts are the targets for inflammation in primary biliary cirrhosis (PBC), but their pathogenesis is not known. Gram-positive bacterial DNA was detected recently in gallbladder bile of PBC patients. In the present study, we assessed the possible pathological role of lipoteichoic acid (LTA), the Gram-positive bacterial cell wall component, in PBC.Methods: Liver samples, obtained from 20 patients with PBC (stage 1–2 with CNSDC: stage 3–4 with loss of bile ducts = 10:10) and from 13 patients with chronic hepatitis due to hepatitis C virus (CH–C) with lymphocytic cholangitis, were subjected to immunohistochemical staining with polyclonal rabbit anti-LTA as the primary antibody. Serum reactivities to LTA were studied by ELISA. After 1 μg of purified LTA was placed in a 96-well microplate as an antigen, an antibody capture assay was carried out using serum samples from PBC (n = 20), CH–C (n = 13) and healthy subjects (n = 11).Results: LTA was localized around the sites of chronic non-suppurative destructive cholangitis (CNSDC) in the portal area in stage 1–2 PBC but was not detected in the portal area in CH–C. In stage 3–4 PBC, LTA was localized around sites of ductular proliferation at the periphery of portal tracts. IgM class anti-LTA serum titers were significantly higher in PBC than in CH–C. IgA class anti-LTA serum titers were significantly higher in PBC than in healthy subjects.Conclusions: In the PBC livers, the profile of immunoreactivity to LTA changed markedly as the disease progressed. Sera from PBC showed higher levels of anti-LTA titers than CH–C (IgM) or from healthy subjects (IgA). The LTA-mediated immune system might affect the initiation and/or progression of PBC. 相似文献
53.
Autoimmune hepatitis type 2 (AIH-2) is a severe autoimmune liver disease with unknown etiology. We recently developed the CYP2D6 mouse model for AIH-2, in which mice are challenged with an adenovirus (Ad-2D6) expressing human cytochrome P450 2D6 (hCYP2D6), the major autoantigen in AIH-2. Such mice develop chronic hepatitis with cellular infiltrations and generation of hCYP2D6-specific antibodies and T cells. Importantly, the CYP2D6 model represents the only model displaying chronic fibrosis allowing for a detailed investigation of the mechanisms of chronic autoimmune-mediated liver fibrogenesis. We found that hCYP2D6-dependent chronic activation of hepatic stellate cells (HSC) resulted in an increased extracellular matrix deposition and elevated expression of α-smooth muscle actin predominantly in and underneath the liver capsule. The route of Ad-2D6 infection dramatically influenced the activation and trafficking of inflammatory monocytes, NK cells and hCYP2D6-specific T cells. Intraperitoneal Ad-2D6 infection caused subcapsular fibrosis and persistent clustering of inflammatory monocytes. In contrast, intravenous infection caused an accumulation of hCYP2D6-specific CD4 T cells throughout the liver parenchyma and induced a strong NK cell response preventing chronic HSC activation and fibrosis. In summary, we found that the location of the initial site of inflammation and autoantigen expression caused a differential cellular trafficking and activation and thereby determined the outcome of AIH-2-like hepatic damage and fibrosis. 相似文献
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56.
A. Ahmad R. Heijke P. Eriksson L. Wirestam S. Kechagias C. Dahle C. Sjwall 《Clinical and experimental immunology》2021,203(1):22-31
Knowledge of concomitant autoimmune liver diseases (AILD) is more detailed in primary Sjögren’s syndrome (pSS) compared to systemic lupus erythematosus (SLE). Herein, the prevalence of autoantibodies associated with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) was investigated in stored sera from patients with SLE (n = 280) and pSS (n = 114). Antibodies against mitochondria (AMA), liver–kidney microsomal (LKM) antigen, smooth muscle (SMA) and anti‐nuclear antibodies (ANA) were analysed with immunofluorescence microscopy. In addition, AILD‐associated autoantibodies were tested with immunoblot. Prior to sampling, eight SLE (2·9%) and three pSS (2·6%) cases were diagnosed with AILD. Among SLE‐cases without known AILD (n = 272), 26 (9·6%) had PBC‐associated autoantibodies, 15 (5·5%) AIH‐associated autoantibodies (excluding ANA) and one serological overlap. Most subjects with PBC‐associated autoantibodies had liver enzymes within reference limits (22 of 27, 81%) or mild laboratory cholestasis (two of 27, 7·4%), while one fulfilled the diagnostic PBC‐criteria. AMA‐M2 detected by immunoblot was the most common PBC‐associated autoantibody in SLE (20 of 272, 7·4%). The prevalence of SMA (4·4%) was comparable with a healthy reference population, but associated with elevated liver enzymes in four of 12 (25%), none meeting AIH‐criteria. The patient with combined AIH/PBC‐serology had liver enzymes within reference limits. Among pSS cases without known AILD (n = 111), nine (8·1%) had PBC‐associated, 12 (10·8%) AIH‐associated autoantibodies and two overlapped. PBC‐associated autoantibodies were found as frequently in SLE as in pSS but were, with few exceptions, not associated with laboratory signs of liver disease. Overall, AILD‐associated autoantibodies were predominantly detected by immunoblot and no significant difference in liver enzymes was found between AILD autoantibody‐negative and ‐positive patients. 相似文献
57.
Risa Kanai Aya Miyagawa-Hayashino Yukiko Shishido-Hara Naoya Nakamura Ikoi Omatsu Yukiko Morinaga Yuji Shimura Junya Kuroda Tetsuya Imura Kyoko Itoh Eiichi Konishi 《Pathology international》2021,71(1):96-101
The case of 70-year-old man with mantle cell lymphoma (MCL) carrying t(11;14) translocation that relapsed as nodal lymphoma combining MCL and classic Hodgkin lymphoma (cHL) 9 years after autologous peripheral blood stem cell transplant (auto-PBSCT) is reported. Lymph nodes contained two separate areas of MCL and cHL-like components. Hodgkin and Reed–Sternberg (HRS)-like cells were accompanied by a prominent histiocyte background. HRS-like cells were CD5−, CD15+, CD20−, CD30+, PAX5+, Bob.1−, Oct2− and EBER+. The MCL component expressed cyclin D1 and SOX11, whereas cyclin D1 and SOX11 expressions were reduced and lost, respectively, in HRS-like cells. Polymerase chain reaction results showed a single clonal rearrangement of the IGH gene in MCL and cHL-like components. CCND1 break apart fluorescence in situ hybridization showed split signals in both MCL and HRS-like cells, suggesting that MCL and cHL-like components were clonally related. Acquisition of p53 expression and Epstein–Barr virus (EBV)-positivity was seen in HRS-like cells. The patient died of disease progression with elevated hepatobiliary enzymes. The autopsy showed both MCL and cHL-like components around the bile ducts, splenic white pulp and bone marrow. The two components were phenotypically distinct, but genetically related, suggesting that transformation of MCL to HRS-like cells during the course of MCL in association with EBV infection. 相似文献
58.
Meta‐analysis of Duct‐to‐duct versus Roux‐en‐Y biliary reconstruction following liver transplantation for primary sclerosing cholangitis
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Sanjay Pandanaboyana Richard Bell Adam J. Bartlett John McCall Ernest Hidalgo 《Transplant international》2015,28(4):485-491
This meta‐analysis aimed to compare outcomes following bile duct reconstruction in patients with primary sclerosing cholangitis (PSC) undergoing liver transplantation depending on whether duct‐to‐duct or Roux‐en‐Y anastomosis was utilized. An electronic search was performed of the MEDLINE, EMBASE, PubMed databases using both subject headings (MeSH) and truncated word searches. Pooled risk ratios and mean difference were calculated using the fixed‐effects and random‐effects models for meta‐analysis. Ten studies including 910 patients met the inclusion criteria. There was no difference in the overall incidence of biliary strictures between the two groups [odds ratio (OR) 1.06 (0.68, 1.66); (P = 0.80)]. The anastomotic stricture rate was similar, [OR 1.18 (0.56, 2.50); (P = 0.67)]. Ascending cholangitis was higher in the Roux–en‐Y group [OR 2.91 (1.17, 7.23); (P = 0.02)]. Anastomotic bile leak rates, graft survival, PSC recurrence and number of patients diagnosed with cholangiocarcinoma following transplantation were comparable between both groups. Duct‐to‐duct and Roux‐en‐Y reconstruction had comparable outcomes. Both techniques are associated with similar incidence of biliary stricture. The bilioenteric reconstruction was associated with a higher risk of cholangitis. The incidence of de novo cholangiocarcinoma was similar in both groups. Duct‐to‐duct reconstruction should be considered when feasible in patients with PSC. 相似文献
59.
Wael El-Matary Stephen L. Guthery Achiya Z. Amir Matthew DiGuglielmo Laura G. Draijer Katryn N. Furuya Nitika Gupta Jessica T. Hochberg Simon Horslen Nanda Kerkar Bart G.P. Koot Trevor J. Laborda Kathleen M. Loomes Cara Mack Mercedes Martinez Alexander Miethke Tamir Miloh Douglas Mogul Mark R. Deneau 《Clinical gastroenterology and hepatology》2021,19(5):1067-1070.e2
60.
【摘要】 目的 介绍急性重症胆管炎治疗体会。方法〓回顾性分析我院2008~2013年收治124例急性重症胆管炎患者的临床资料。结果〓手术治疗组112例,109例痊愈,其中81例术后一个月拔除T管痊愈出院,4例因肝内胆管残留结石二期行肝切除术,肝内胆管及胆总管有残石14例,胆总管有残石6例二期手术行经T管胆道镜取石痊愈,PTCD(经皮经肝穿刺胆管引流术)2例,ENBD(经鼻胆管引流)2例。手术后死亡3例,其中1例PTCD后因多器官功能衰竭而死亡,2例胆囊造瘘术后因感染性休克而死亡。非手术组12例中有8例采取保守治疗成功后行二期手术痊愈,4例因多器官功能衰竭而死亡。结论〓急性重症胆管炎应早期诊断,手术治疗是首选方案,应选择快速、简单、有效的手术方法。 相似文献