全文获取类型
收费全文 | 1413篇 |
免费 | 53篇 |
国内免费 | 15篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 3篇 |
妇产科学 | 10篇 |
基础医学 | 203篇 |
口腔科学 | 29篇 |
临床医学 | 94篇 |
内科学 | 598篇 |
皮肤病学 | 17篇 |
神经病学 | 70篇 |
特种医学 | 15篇 |
外科学 | 210篇 |
综合类 | 19篇 |
预防医学 | 55篇 |
眼科学 | 9篇 |
药学 | 49篇 |
中国医学 | 5篇 |
肿瘤学 | 93篇 |
出版年
2023年 | 13篇 |
2022年 | 17篇 |
2021年 | 33篇 |
2020年 | 15篇 |
2019年 | 18篇 |
2018年 | 14篇 |
2017年 | 14篇 |
2016年 | 16篇 |
2015年 | 21篇 |
2014年 | 46篇 |
2013年 | 47篇 |
2012年 | 63篇 |
2011年 | 89篇 |
2010年 | 52篇 |
2009年 | 45篇 |
2008年 | 62篇 |
2007年 | 98篇 |
2006年 | 98篇 |
2005年 | 101篇 |
2004年 | 88篇 |
2003年 | 80篇 |
2002年 | 68篇 |
2001年 | 58篇 |
2000年 | 63篇 |
1999年 | 61篇 |
1998年 | 19篇 |
1997年 | 18篇 |
1996年 | 20篇 |
1995年 | 16篇 |
1994年 | 12篇 |
1993年 | 6篇 |
1992年 | 20篇 |
1991年 | 8篇 |
1990年 | 10篇 |
1989年 | 6篇 |
1988年 | 11篇 |
1987年 | 11篇 |
1986年 | 7篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 8篇 |
1975年 | 5篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1970年 | 3篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1966年 | 2篇 |
1965年 | 1篇 |
排序方式: 共有1481条查询结果,搜索用时 0 毫秒
1.
Kei Kamide Yoshihiro Kokubo Hironori Hanada Junko Nagura Jin Yang Shin Takiuchi Chihiro Tanaka Mariko Banno Yoshikazu Miwa Masayoshi Yoshii Tetsutaro Matayoshi Hisayo Yasuda Takeshi Horio Akira Okayama Hitonobu Tomoike Yuhei Kawano Toshiyuki Miyata 《Hypertension research》2006,29(4):243-252
Mutations in the gene encoding 11beta-hydroxysteroid dehydrogenase type 2, HSD11B2, cause a rare monogenic juvenile hypertensive syndrome called apparent mineralocorticoid excess (AME). In AME, defective HSD11B2 enzyme activity results in overstimulation of the mineralocorticoid receptor (MR) by cortisol, causing sodium retention, hypokalemia, and salt-dependent hypertension. Here, we have studied whether genetic variations in HDS11B2 are implicated in essential hypertension in Japanese hypertensives and the general population. By sequencing the entire coding region and the promoter region of HDS11B2 in 953 Japanese hypertensives, we identified five missense mutations in 11 patients (L14F, n = 5; R74H, n = 1; R147H, n = 3; T156I, n = 1; R335H, n = 1) and one novel frameshift mutation (4884Gdel, n = 1) in a heterozygous state, in addition to 19 genetic variations. All genetic variations identified were rare, with minor allele frequencies less than 0.005. Four of 12 patients with the missense/frameshift mutations showed renal failure. Four missense mutations, L14F, R74H, R147H, and R335H, were successfully genotyped in the general population, with a sample size of 3,655 individuals (2,175 normotensives and 1,480 hypertensives). Mutations L14F, R74H, R147H, and R335H were identified in hypertensives (n = 6, 8, 3, and 0, respectively) and normotensives (n = 8, 12, 5, and 0, respectively) with a similar frequency, suggesting that these missense mutations may not strongly affect the etiology of essential hypertension. Since the allele frequency of all of the genetic variations identified in this study was rare, an association study was not conducted. Taken together, our results indicate that missense mutations in HSD11B2 do not substantially contribute to essential hypertension in Japanese. 相似文献
2.
Yoshinobu Okabe Osamu Tsuruta Yoshiki Naito Hideya Suga Michio Sata 《Digestive endoscopy》2007,19(Z1):S121-S125
Regarding peroral cholangioscopy (POCS) for biliary disease, due to the recent appearance of a video cholangioscope that can obtain high‐quality images, it is possible to observe subtle changes of the biliary mucosa. In addition to the conventional observation method using POCS, the biliary mucosa with also observed with narrow band imaging (NBI) in one case of chronic cholangitis and four cases of extra hepatic bile duct tumor (three surgical cases). In the conventional observation method, the vessels in the surface layer of the biliary mucosa could be observed more clearly using NBI. In one case in which a tumor was observed, the irregularity of the biliary mucosa became clear on NBI, and the vessels inside a papillary tumor could also be easily observed. In another case of bile duct tumor, the conventional observation method showed a region in the proximity of the tumor where the vessels could not be seen clearly, but they could be seen clearly on NBI. In all of the cases, the bile juice was seen as red on NBI, which disturbed the observation. With POCS using NBI, it was possible to observe the vessels and irregularities in the surface layer of the biliary mucosa more clearly than with conventional observation methods. 相似文献
3.
Kazuta Fukumori Yoichi Yano Koutaro Kuwaki Shuji Sumie Eiji Ando Masatoshi Tanaka Michio Sata 《Nihon Shokakibyo Gakkai zasshi》2007,104(8):1225-1230
A 64-year-old man was admitted for further examinations of a liver tumor. The patient was diagnosed as chronic hepatitis C complicated with advanced hepatocelluar carcinoma (HCC) with left portal vein tumor thrombosis. As he refused surgical treatment, hepatic arterial infusion chemotherapy (HAIC) using cisplatin and 5-fluorouracil was performed initially. Administration of ursodesoxycholic acid (UDCA) was also started. Following HAIC, microwave coagulation therapy for residual tumor was added. Consequently, viable lesions of HCC disappeared completely. At present, after more than 8 years, neither signs of tumor recurrence, nor elevation of hepatic enzymes has been observed. Although the precise reason for long survival of this patient is not known, we speculate that suppression of levels of hepatic enzymes, as well as HAIC for subclinical intrahepatic metastasis, contributed to the good outcome. Therapeutic strategy for hepatic inflammation seems to be important for long-term prevention of hepatocarcinogenesis. 相似文献
4.
Hirofumi Fukushima Emiko Katou Kouji Nagayama Akira Shirachi Michio Sata 《Nihon Shokakibyo Gakkai zasshi》2006,103(6):661-666
A 80-year old man was referred to our hospital because of an elevation of serum amylase level. Diffuse enlargement of the pancreas was detected by abdominal computed tomography, and also diffuse narrowing of the main pancreatic duct was revealed using endoscopic retrograde cholangiopancreatography. The serum level of IgG was elevated to 3450mg/dl. Besides, on the 10th hospital day, petechia developed and the platelet level decreased to 1.5 x 10(4)/microl. The platelet-associated IgG, antiplatelet antibody and antinuclear antibody in serum were positive. The levels of serum complements were low. From all these findings the patient was diagnosed as autoimmune pancreatitis complicated with immune thrombocytopenia. The treatment with prednisolone was started, which was effective on each disease. The medication was suspended a year ago, and so far there is no data suggesting the recurrence of autoimmune pancreatitis or immune thrombocytopenia. 相似文献
5.
6.
Sadataka Inuzuka Takato Ueno Hideo Tateishi Takuji Torimura Michio Sata Kyuichi Tanikawa Masamichi Kojiro 《Pathology international》1994,44(5):391-397
Elevation of the serum angiotensin-converting enzyme (sACE) level and hepatic granulomas were found during a clinical relapse in a 22 year old patient with acute viral hepatitis type A (AVH-A). The serum transaminase level and sACE level remained high for more than 6 months. In the biopsied specimen of the liver, fibrous rings of granulomas composed of collagen types I, III, and V were observed. Furthermore, the localization of ACE was visible in the rough endoplasmic reticulum of epithelioid cells of granulomas in the liver under electron microscopy using the indirect immunoperoxidase method. These results suggest that granuloma cells in the liver caused by hepatitis A may be involved in ACE production. In addition, other diseases associated with the presence of granulomas in the liver, such as lymphoma, cytomegalovirus infection, visceral leishmaniasis, and lupoid hepatitis, were ruled out. However, the hepatic granulomas disappeared with the healing of AVH-A. In this regard, the present case is considered to be one of the very few cases of hepatic sarcoidosis. 相似文献
7.
8.
Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 3 总被引:15,自引:0,他引:15
下载免费PDF全文
![点击此处可从《The American journal of pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Kawaguchi T Yoshida T Harada M Hisamoto T Nagao Y Ide T Taniguchi E Kumemura H Hanada S Maeyama M Baba S Koga H Kumashiro R Ueno T Ogata H Yoshimura A Sata M 《The American journal of pathology》2004,165(5):1499-1508
The pathogenesis of hepatitis C virus (HCV)-associated insulin resistance remains unclear. Therefore, we investigated mechanisms for HCV-associated insulin resistance. Homeostasis model assessment for insulin resistance was increased in patients with HCV infection. An increase in fasting insulin levels was associated with the presence of serum HCV core, the severity of hepatic fibrosis and a decrease in expression of insulin receptor substrate (IRS) 1 and IRS2, central molecules of the insulin-signaling cascade, in patients with HCV infection. Down-regulation of IRS1 and IRS2 was also seen in HCV core-transgenic mice livers and HCV core-transfected human hepatoma cells. Carbobenzoxy-l-leucyl-l-leucyl-l-leucinal, a potent proteosomal proteolysis inhibitor, blocked down-regulation of IRS1 and IRS2 in HCV core-transfected hepatoma cells. In human hepatoma cells, HCV core up-regulated suppressor of cytokine signaling (SOCS) 3 and caused ubiquitination of IRS1 and IRS2. HCV core-induced down-regulation of IRS1 and IRS2 was not seen in SOCS3(-/-) mouse embryonic fibroblast cells. Furthermore, HCV core suppressed insulin-induced phosphorylation of p85 subunit of phosphatidylinositol 3-kinase and Akt, activation of 6-phosphofructo-2-kinase, and glucose uptake. In conclusion, HCV infection changes a subset of hepatic molecules regulating glucose metabolism. A possible mechanism is that HCV core-induced SOCS3 promotes proteosomal degradation of IRS1 and IRS2 through ubiquitination. 相似文献
9.
Expression and localization of human herpesvirus 8-encoded proteins in primary effusion lymphoma, Kaposi's sarcoma, and multicentric Castleman's disease 总被引:14,自引:0,他引:14
To investigate the expression of human herpesvirus 8 (HHV8)-encoded proteins in the cells of primary effusion lymphoma (PEL), Kaposi's sarcoma (KS) and multicentric Castleman's disease (MCD), nine rabbit polyclonal antibodies to K2, ORF26, K8, K8.1, K10, K11, ORF59, ORF65, and ORF73 were developed. Western blot analysis in PEL cell lines (TY-1 and BCBL-1) revealed that the expression of these proteins, except ORF73 (LANA), was induced by tetradecanoylphorbol acetate (TPA) treatment, indicating that these proteins are lytic proteins. Immunofluorescence assay in primary PEL cells derived from pericardial effusion and PEL cell lines with and without TPA treatment revealed that primary PEL cells exhibited the same expression pattern as noninduced PEL cell lines, and the treatment changed localization of K8, ORF59, and ORF65 proteins. Immunohistochemistry revealed that 90% of KS spindle cells expressed the ORF73 protein, whereas a small population of KS cells expressed K8, K10, K11, ORF59, and ORF65 proteins. In MCD, ORF73, ORF59, K8, K2, and K10 proteins were expressed in the cells at mantle zone of the follicle. These data indicate that KS and PEL cells expressed predominantly latent proteins, whereas MCD expressed both latent and lytic proteins, suggesting that HHV8 plays a different role in the pathogenesis of HHV8-associated diseases. 相似文献
10.
Koga H Sakisaka S Yoshitake M Harada M Kumemura H Hanada S Taniguchi E Kawaguchi T Kumashiro R Sata M 《International journal of molecular medicine》2002,9(6):621-626
Primary sclerosing cholangitis (PSC) is known to be frequently associated with inflammatory bowel diseases. In a rat with self-filling blind loop (SFBL), a proposed animal model for PSC, hepatobiliary inflammation has previously been demonstrated. In this study, we assessed the involvement of lipopolysaccharide (LPS), a bacterial endotoxin, in the pathogenesis of hepatobiliary inflammation of the SFBL model. The hepatic localization of LPS was examined by immunohistochemistry using an anti-lipid A antibody. The portal blood concentration of LPS was measured by an endotoxin-specific chromogenic Limulus test (Endospecy test). LPS was localized in the biliary epithelial cells (BECs) of rats with SFBL, and the portal blood concentration of LPS was significantly higher than that of sham-operated rats. Development of hepatobiliary inflammation, peribiliary fibrosis, and injury to the intestinal mucosa were histologically confirmed. Constriction in the biliary trees was radiologically demonstrated. These findings suggested that abnormal accumulation of LPS, which may be derived from portal blood, in BECs was involved in the pathogenesis of hepatobiliary inflammation with intestinal injury. 相似文献