全文获取类型
收费全文 | 10309篇 |
免费 | 496篇 |
国内免费 | 92篇 |
专业分类
耳鼻咽喉 | 99篇 |
儿科学 | 176篇 |
妇产科学 | 78篇 |
基础医学 | 1150篇 |
口腔科学 | 198篇 |
临床医学 | 548篇 |
内科学 | 3115篇 |
皮肤病学 | 154篇 |
神经病学 | 735篇 |
特种医学 | 436篇 |
外科学 | 1728篇 |
综合类 | 45篇 |
预防医学 | 274篇 |
眼科学 | 173篇 |
药学 | 731篇 |
中国医学 | 14篇 |
肿瘤学 | 1243篇 |
出版年
2024年 | 12篇 |
2023年 | 67篇 |
2022年 | 125篇 |
2021年 | 259篇 |
2020年 | 141篇 |
2019年 | 184篇 |
2018年 | 241篇 |
2017年 | 197篇 |
2016年 | 245篇 |
2015年 | 261篇 |
2014年 | 331篇 |
2013年 | 386篇 |
2012年 | 660篇 |
2011年 | 669篇 |
2010年 | 359篇 |
2009年 | 360篇 |
2008年 | 654篇 |
2007年 | 725篇 |
2006年 | 689篇 |
2005年 | 697篇 |
2004年 | 683篇 |
2003年 | 627篇 |
2002年 | 637篇 |
2001年 | 132篇 |
2000年 | 136篇 |
1999年 | 138篇 |
1998年 | 142篇 |
1997年 | 104篇 |
1996年 | 89篇 |
1995年 | 93篇 |
1994年 | 73篇 |
1993年 | 58篇 |
1992年 | 89篇 |
1991年 | 71篇 |
1990年 | 65篇 |
1989年 | 57篇 |
1988年 | 59篇 |
1987年 | 67篇 |
1986年 | 47篇 |
1985年 | 50篇 |
1984年 | 41篇 |
1983年 | 26篇 |
1982年 | 23篇 |
1981年 | 12篇 |
1980年 | 12篇 |
1979年 | 20篇 |
1978年 | 13篇 |
1977年 | 9篇 |
1976年 | 11篇 |
1975年 | 7篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
71.
Dual-probe assay for rapid detection of drug-resistant Mycobacterium tuberculosis by real-time PCR 总被引:3,自引:0,他引:3
下载免费PDF全文
![点击此处可从《Journal of clinical microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Wada T Maeda S Tamaru A Imai S Hase A Kobayashi K 《Journal of clinical microbiology》2004,42(11):5277-5285
Mutations in particular nucleotides of genes coding for drug targets or drug-converting enzymes lead to drug resistance in Mycobacterium tuberculosis. For rapid detection of drug-resistant M. tuberculosis in clinical specimens, a simple and applicable method is needed. Eight TaqMan minor groove binder (MGB) probes, which discriminate one-base mismatches, were designed (dual-probe assay with four reaction tubes). The target of six MGB probes was the rpoB gene, which is involved in rifampin resistance; five probes were designed to detect for mutation sites within an 81-bp hot spot of the rpoB gene, and one probe was designed as a tuberculosis (TB) control outside the rpoB gene hot-spot. We also designed probes to examine codon 315 of katG and codon 306 of embB for mutations associated with resistance to isoniazid and ethambutol, respectively. Our system was M. tuberculosis complex specific, because neither nontuberculous mycobacteria nor bacteria other than mycobacteria reacted with the system. Detection limits in direct and preamplified analyses were 250 and 10 fg of genomic DNA, respectively. The system could detect mutations of the rpoB, katG, and embB genes in DNAs extracted from 45 laboratory strains and from sputum samples of 27 patients with pulmonary TB. This system was much faster (3 h from DNA preparation) than conventional drug susceptibility testing (3 weeks). Results from the dual-MGB-probe assay were consistent with DNA sequencing. Because the dual-probe assay system is simple, rapid, and accurate, it can be applied to detect drug-resistant M. tuberculosis in clinical laboratories. 相似文献
72.
HLA-DRB1*1602 allele is positively associated with HPV cervical infection in Bolivian Andean women 总被引:3,自引:0,他引:3
Cervantes J Lema C Valentina Hurtado L Andrade R Hurtado Gomez L Torrico L Zegarra L Quiroga G Asturizaga D Dulon A Prada R Panoso W Yashiki S Fujiyoshi T Sonoda S 《Human immunology》2003,64(9):890-895
Incidence of cervical cancer is high among Bolivian Andean women. Human papillomavirus (HPV) infection is known as the major risk factor of cervical cancer. The host immune system plays an important role in the outcome of HPV infection and associated malignancies. In order to study the immunogenetic background of Bolivian Andean women with regard to HPV infection status, we compared HLA class I and class II allele frequencies between 37 HPV positive and 68 HPV negative Bolivian women. Demographic variables, including distribution of Andean ethnicities, were similar in both groups. Comparison of HLA class I allele frequencies between both groups indicated no significant difference. In contrast, HLA class II DRB1*1602 allele, an Amerindian allele, was significantly higher in the HPV positive women compared with HPV negative controls (chi(2) = 5.2, p < 0.05, odds ratio = 3.17; 95% confidence interval = 1.4-8.8). HPV types present in the HPV positive group were HPV-18, -16, -31, -33, and -58. These results suggest that HLA class II DRB1*1602 may confer susceptibility to infection with genetically related HPV types. This is the first report of an HLA class II association with HPV infection in an Andean population. 相似文献
73.
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
74.
75.
Matsumoto S Sasaki T Imamura A Matsuo K Kayashima T Hashida A Ono S Tsujita T Matsumoto S Nakane Y Tokunaga K Okazaki Y 《American journal of medical genetics》2002,114(1):42-45
Several Caucasian studies and one Japanese study have observed associations between human leukocyte antigen (HLA) class I specificities, including A24 (9) and A26 (10) and schizophrenia. Most of those studies were conducted in 1970s and early 1980s, when the typing technique of HLA was not adequately reliable. Also, an operational diagnostic system was not employed in many of the studies. The present study investigated frequencies of HLA-A specificities in schizophrenia patients (ICD-10 and DSM-III-R, n=98) and sex-matched healthy controls (n=392) from population in the southwestern part of Japan. HLA-B and -C specificities were studied in addition. Frequencies of subjects possessing A24 and A26 were not different between the patients and controls (54% and 24% in the patients and 62% and 24% in the controls, respectively). No significant difference was found in frequencies of other class I (A, B, and C) specificities between the patients and the controls. Thus, the present study provided no evidence for an association between the HLA class I specificities, including A24, A26, and others, and schizophrenia in the Japanese population. 相似文献
76.
Kawabata A Kawao N Itoh H Shimada C Takebe K Kuroda R Masuko T Kataoka K Ogawa S 《Neuroscience letters》2002,329(3):349-353
Activation of the peripheral protease-activated receptor-2 (PAR-2) triggers nociceptive behaviour and thermal hyperalgesia in rats. The present study created a novel mouse model for PAR-2-triggered nociception, and then examined the roles of NMDA receptors and the nitric oxide (NO) pathway in nociceptive processing by PAR-2. Intraplantar administration of the PAR-2 agonist SLIGRL-NH(2) elicited nociceptive responses in mice, an effect being more specific in mast cell-depleted mice. This PAR-2-triggered nociception was abolished by the NMDA receptor antagonist MK-801, but not the neuronal NO synthase inhibitor 7-nitro indazole. In contrast, the PAR-2-triggered thermal hyperalgesia in rats was blocked by both agents. Our study thus provides a novel mouse model for PAR-2-mediated nociception, and suggests that NMDA receptors are involved in PAR-2-triggered nociception and hyperalgesia, while NO contributes only to the latter. 相似文献
77.
Takaaki Ohmori Kazuyo Okada Ryo Tabei Keisuke Sugiura Shinji Nabeshima Hiroji Ohoka Masaki Okamoto 《Pathology international》1994,44(4):333-337
A case of primary seminal vesicle carcinoma is reported. The tumor was a CA125-producing adenocarcinoma consisting of fine papillary-tubular, intricate branching or anastomosing glandular structures and was composed of small cuboidal, but occasionally hobnailed, cells with mostly clear, but occasionally granular, cytoplasm. Some tumor cells showed evidence of secretion of seromucinous materials into the interpapillary and cystic space. lmmunohistochemically, almost half of the tumor cells expressed a positive reaction with anti-CAl25, a common serological marker for ovarian epithelial carcinomas; however, no tumor cells expressed any other serological tumor markers such as carcinoem-bryonic antigen, α-fetoprotein, human chorionic gonadotropin, prostatic specific acid phosphatase, or prostatic specific antigen. The patient showed a high level of serological CA125, which fluctuated parallel with the growth, removal and recurrence of the tumor. The morphological and immunohistochemical findings suggested a close relationship between the present tumor and clear cell carcinoma of the ovary, which is thought to be of a Müllerian-Wolfian duct origin. 相似文献
78.
Massimo Pignatelli Tareq W. Ansari Pat Gunter Dan Liu Shinji Hirano Masatoshi Takeichi Günter Klppel Nicholas R. Lemoine 《The Journal of pathology》1994,174(4):243-248
Epithelial cadherin (E-cadherin) is a Ca2+-dependent cell-cell adhesion molecule that connects cells via homotypic interactions. Its function is critical in the induction and maintenance of cell polarity and differentiation, and its loss of downregulation is associated with an invasive and poorly differentiated phenotype in colon and other tumours. We have used an avidin-biotin immunoperoxidase technique to localize E-cadherin in microwave-treated, paraffin-embedded sections from 36 patients with pancreatic adenocarcinomas. E-cadherin was expressed by normal ductal and acinar cells with typical membranous staining at the intercellular junctions. Loss of normal surface E-cadherin expression was found in 19/36 (53 per cent) tumours compared to the adjacent normal ductal cells. Abnormal E-cadherin expression was found more frequently in poorly differentiated (grade III) (6/7, 86 per cent) than in well-differentiated tumours (grade I) (4/14, 28 per cent) (P=0·012). Membranous E-cadherin expression was also lost more frequently in primary tumours with lymph node (stage III) (14/23, 61 per cent) and distant metastasis (stage IV) (2/2, 100 per cent) compared with 3/11 (27 per cent) lymph node-negative tumours (stage I) (P=0·043). In conclusions, our data indicate that loss of membranous E-cadherin expression is associated with high grade and advanced stage in pancreatic cancer. 相似文献
79.
80.
Interaction of cholecystokinin (CCK) with vasoactive intestinal peptide (VIP) in body shaking response to ice-water immersion was observed in pentobarbital-anesthetized rats. Although CCK itself had no influence on the response, VIP suppressed it and this effect of VIP was antagonized by simultaneous administration of sulfated octapeptide of CCK, but not by non-sulfated CCK. 相似文献