全文获取类型
收费全文 | 389篇 |
免费 | 31篇 |
国内免费 | 12篇 |
专业分类
儿科学 | 4篇 |
妇产科学 | 3篇 |
基础医学 | 44篇 |
口腔科学 | 3篇 |
临床医学 | 12篇 |
内科学 | 67篇 |
皮肤病学 | 70篇 |
神经病学 | 17篇 |
特种医学 | 3篇 |
外科学 | 13篇 |
综合类 | 18篇 |
预防医学 | 11篇 |
眼科学 | 20篇 |
药学 | 92篇 |
中国医学 | 2篇 |
肿瘤学 | 53篇 |
出版年
2023年 | 5篇 |
2021年 | 7篇 |
2020年 | 5篇 |
2019年 | 12篇 |
2018年 | 9篇 |
2017年 | 12篇 |
2016年 | 6篇 |
2015年 | 17篇 |
2014年 | 21篇 |
2013年 | 33篇 |
2012年 | 21篇 |
2011年 | 26篇 |
2010年 | 24篇 |
2009年 | 24篇 |
2008年 | 20篇 |
2007年 | 13篇 |
2006年 | 20篇 |
2005年 | 28篇 |
2004年 | 18篇 |
2003年 | 27篇 |
2002年 | 14篇 |
2001年 | 14篇 |
2000年 | 8篇 |
1999年 | 16篇 |
1998年 | 2篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1979年 | 1篇 |
1978年 | 1篇 |
排序方式: 共有432条查询结果,搜索用时 31 毫秒
11.
Hepatocellular carcinoma (HCC) often develops in patients with chronic liver diseases associated with hepatitis B (HBV) and hepatitis C (HCV) virus infections with high incidences. Particularly, post-therapeutic recurrence encountered after the curative treatment of the preceding HCC may limit the prognosis. Thus, prevention of HCC is of great significance. In the present review, immunopreventions with alpha-interferon and glycyrrhizin, as well as chemoprevention with acyclic retinoid, are discussed. alpha-Interferon prevents the development of HCC not only in patients with a long-term elimination of HCV (sustained virological responders), but in ones with normalized serum aminotransferases (sustained biochemical responders). Glycyrrhizin also suppresses serum aminotransferases and thereby prevents the tumor development, even though the compound does not have antiviral activity for HBV or HCV by itself. Therefore, suppression of hepatic necroinflammation by these drugs may serve to prevent hepatocarcinogenesis. In contrast, acyclic retinoid suppresses the post-therapeutic recurrence in cirrhotic patients who underwent curative treatment of preceding tumors. The retinoid induces the disappearance of serum lectin-reactive alpha-fetoprotein (AFP-L3), a tumor marker indicating the presence of unrecognizable tumors in the remnant liver, suggesting a deletion of such minute (pre)malignant clones (clonal deletion). As a molecular mechanism of the clonal deletion, a novel mechanism of apoptosis induction by the retinoid via tissue transglutaminase is implicated. In future, a combination of immunopreventive and chemopreventive therapies may give a clue to the further advances of cancer prevention, and thereby to the improvement of the prognosis of cirrhotic patients. 相似文献
12.
13.
Human exposure to arsenic in drinking water is a widespread public health concern, and such exposure is known to be associated with many human diseases. The detailed molecular mechanisms about how arsenic species contribute to the adverse human health effects, however, remain incompletely understood. Monomethylarsonous acid [MMA(III)] is a highly toxic and stable metabolite of inorganic arsenic. To exploit the mechanisms through which MMA(III) exerts its cytotoxic effect, we adopted a quantitative proteomic approach, by coupling stable isotope labeling by amino acids in cell culture (SILAC) with LC-MS/MS analysis, to examine the variation in the entire proteome of GM00637 human skin fibroblasts following acute MMA(III) exposure. Among the ~ 6500 unique proteins quantified, ~ 300 displayed significant changes in expression after exposure with 2 μM MMA(III) for 24 h. Subsequent analysis revealed the perturbation of de novo cholesterol biosynthesis, selenoprotein synthesis and Nrf2 pathways evoked by MMA(III) exposure. Particularly, MMA(III) treatment resulted in considerable down-regulation of several enzymes involved in cholesterol biosynthesis. In addition, real-time PCR analysis showed reduced mRNA levels of select genes in this pathway. Furthermore, MMA(III) exposure contributed to a distinct decline in cellular cholesterol content and significant growth inhibition of multiple cell lines, both of which could be restored by supplementation of cholesterol to the culture media. Collectively, the present study demonstrated that the cytotoxicity of MMA(III) may arise, at least in part, from the down-regulation of cholesterol biosynthesis enzymes and the resultant decrease of cellular cholesterol content. 相似文献
14.
15.
16.
Mathilde Raverdeau Aurore Gely-Pernot Betty Féret Christine Dennefeld Gérard Benoit Irwin Davidson Pierre Chambon Manuel Mark Norbert B. Ghyselinck 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(41):16582-16587
Direct evidence for a role of endogenous retinoic acid (RA), the active metabolite of vitamin A in the initial differentiation and meiotic entry of spermatogonia, and thus in the initiation of spermatogenesis is still lacking. RA is synthesized by dedicated enzymes, the retinaldehyde dehydrogenases (RALDH), and binds to and activates nuclear RA receptors (RARA, RARB, and RARG) either within the RA-synthesizing cells or in the neighboring cells. In the present study, we have used a combination of somatic genetic ablations and pharmacological approaches in vivo to show that during the first, prepubertal, spermatogenic cycle (i) RALDH-dependent synthesis of RA by Sertoli cells (SC), the supporting cells of the germ cell (GC) lineage, is indispensable to initiate differentiation of A aligned into A1 spermatogonia; (ii) RARA in SC mediates the effects of RA, possibly through activating Mafb expression, a gene whose Drosophila homolog is mandatory to GC differentiation; (iii) RA synthesized by premeiotic spermatocytes cell autonomously induces meiotic initiation through controlling the RAR-dependent expression of Stra8. Furthermore, we show that RA of SC origin is no longer necessary for the subsequent spermatogenic cycles but essential to spermiation. Altogether, our data establish that the effects of RA in vivo on spermatogonia differentiation are indirect, via SC, but direct on meiotic initiation in spermatocytes, supporting thereby the notion that, contrary to the situation in the female, RA is necessary to induce meiosis in the male. 相似文献
17.
《Medical hypotheses》2014,82(6):1059-1062
Idiopathic intracranial hypertension is a common disorder affecting mainly healthy, young, overweight women. The pathogenesis of this condition is unknown, but it has been shown to follow treatment with several compounds including corticosteroids and vitamin A derivatives. This paper will offer a novel hypothesis and insight on the pathogenesis of drug induced intracranial hypertension following a review and analysis of the literature. Both corticosteroids and vitamin A derivatives have been shown to upregulate the expression of aquaporin 1, a water channel protein. Aquaporin 1 is widely distributed in the human brain and is associated with water secretion into the subarachnoid space. Aquaporin 1 was also shown to participate in the regulation of weight. Agents used for treating idiopathic intracranial hypertension reduce aquaporin 1 expression. Based on these observations, we propose that aquaporin 1 has a pathogenetic role in drug induced idiopathic intracranial hypertension. Over expression of this gene causes increased intracranial pressure, and downregulation reduces pressure and alleviates the symptomatology and complications of idiopathic intracranial hypertension. 相似文献
18.
赵晓红 《国际病理科学与临床杂志》2011,31(3):234-237
维甲酸相关孤核受体α(retinoid acid receptor related orphan receptor α,RORα)是核受体超家族中的一员,广泛分布于机体各组织,具有多种重要的生理功能.近年来,RORα与肿瘤的关系受到越来越多的关注,RORα在肿瘤发生中的作用是目前研究的热点之一.研究表明:RORα的表达... 相似文献
19.
Li Ping YAO Kai Chun WU Han Ping WU Bao Hua SONG Tai Dong QIAO Dai Ming FAN 《Journal of digestive diseases》2002,3(2):51-55
OBJECTIVE: To investigate the expression of peroxisome proliferator‐activated receptor γ (PPAR‐γ) and retinoid X receptor α (RXR‐α) in chronic gastritis, gastric mucosal dysplasia and gastric carcinoma and to identify any correlations between PPAR‐γ and RXR‐α expression in this progression sequence. METHODS: Immunohistochemical methods (avidin? biotin?peroxidase complex) were used to examine the expression of PPAR‐γ and RXR‐α in 53 patients with gastric carcinoma, 18 with gastric mucosal dysplasia and 30 with chronic atrophic gastritis. Thirty‐one patients with chronic non‐atrophic gastritis acted as controls. RESULTS: The positive rates of PPAR‐γ and RXR‐α in gastric carcinoma were 41.5 and 54.7%, 27.8 and 38.9% in gastric mucosal dysplasia, 10.0 and 20.0% in chronic atrophic gastritis, and 6.5 and 16.1% in chronic non‐atrophic gastritis, respectively. The expression of PPAR‐γ and RXR‐α increased during the progression from chronic non‐atrophic gastritis to chronic atrophic gastritis, then to gastric carcinoma. Compared with chronic gastritis, the expression of PPAR‐γ and RXR‐α in gastric mucosal dysplasia and gastric carcinoma was significantly increased (P < 0.05, P < 0.01). In gastric carcinoma, the expression of PPAR‐γ and RXR‐α was not associated with tumor cell differentiation or metastasis in the lymph nodes (P > 0.05). There was a positive correlation between the expression of PPAR‐γ and RXR‐α in gastric carcinoma (r= 0.54, P < 0.01). CONCLUSIONS: Overexpression of PPAR‐γ and RXR‐α protein is apparent in human gastric cancer. This might be an early event in carcinogenesis, and both PPAR‐γ and RXR‐α may play independent and/or synergistic roles in the progression of gastric carcinoma. 相似文献
20.
Ramamoorthy P Thomas S Ramachandran A Balasubramanian KA 《Digestive diseases and sciences》2006,51(3):466-470
Mild heat treatment can modulate metabolism and prevent stress-induced alterations in cells and tissues. Retinoids are known
to influence cellular metabolism and are essential for growth and differentiation, particularlepithelial tissue. This study
examines the effect of mild heat treatment on retinoid alterations in enterocytes in the rat small intestine. Heat treatment
changed the differentiation pattern of enterocytes along the villus-crypt axis, accompanied by increases in retinol, retinaldehyde,
and retinoic acid in proliferating crypt cells. Activities of retinoid metabolizing enzymes such as retinaldehyde oxidase
and retinaldehyde reductase were also increased. These results suggest that mild heat treatment can alter retinoid metabolism
in the small intestine, which might influence epithelial cell proliferation and differentiation.
The Wellcome Trust Research Laboratory is supported by the Wellcome Trust, London. The financial assistance from the Council
of Scientific and Industrial Research, Government of India, is gratefully acknowledged. R.P. and S.T. are senior research
fellows of the Council of Scientific and Industrial Research, Government of India. 相似文献