全文获取类型
收费全文 | 3804篇 |
免费 | 357篇 |
国内免费 | 188篇 |
专业分类
耳鼻咽喉 | 40篇 |
儿科学 | 38篇 |
妇产科学 | 80篇 |
基础医学 | 1233篇 |
口腔科学 | 28篇 |
临床医学 | 195篇 |
内科学 | 691篇 |
皮肤病学 | 75篇 |
神经病学 | 224篇 |
特种医学 | 129篇 |
外科学 | 248篇 |
综合类 | 436篇 |
预防医学 | 154篇 |
眼科学 | 55篇 |
药学 | 301篇 |
中国医学 | 97篇 |
肿瘤学 | 325篇 |
出版年
2023年 | 52篇 |
2022年 | 84篇 |
2021年 | 88篇 |
2020年 | 66篇 |
2019年 | 93篇 |
2018年 | 85篇 |
2017年 | 106篇 |
2016年 | 120篇 |
2015年 | 115篇 |
2014年 | 217篇 |
2013年 | 216篇 |
2012年 | 223篇 |
2011年 | 269篇 |
2010年 | 231篇 |
2009年 | 271篇 |
2008年 | 247篇 |
2007年 | 266篇 |
2006年 | 254篇 |
2005年 | 205篇 |
2004年 | 159篇 |
2003年 | 171篇 |
2002年 | 102篇 |
2001年 | 85篇 |
2000年 | 76篇 |
1999年 | 81篇 |
1998年 | 53篇 |
1997年 | 64篇 |
1996年 | 35篇 |
1995年 | 55篇 |
1994年 | 45篇 |
1993年 | 45篇 |
1992年 | 14篇 |
1991年 | 12篇 |
1990年 | 10篇 |
1989年 | 18篇 |
1988年 | 13篇 |
1987年 | 17篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1984年 | 11篇 |
1983年 | 7篇 |
1982年 | 8篇 |
1981年 | 5篇 |
1980年 | 7篇 |
1979年 | 4篇 |
1978年 | 5篇 |
1975年 | 3篇 |
1974年 | 4篇 |
1972年 | 3篇 |
1969年 | 3篇 |
排序方式: 共有4349条查询结果,搜索用时 15 毫秒
1.
2.
孕烷X受体(Pregnane X receptor,PXR)是核受体家族成员之一,可被多种内源性和外源性物质激活。PXR通过诱导药物代谢酶和转运体,在肝脏、肠道、皮肤和血管内皮中发挥重要的解毒作用。此外,PXR还具有调节糖脂代谢、胆固醇代谢、胆红素和胆汁酸代谢、免疫炎症反应等功能。研究证实,PXR已被公认为多种炎症性疾病的有效药物干预靶点,如炎性结肠炎、坏死性肠炎、肝炎、皮炎、糖尿病等。多种中药或其活性成分可以作为PXR受体激动剂通过核因子B(NF-κB)和尾部相关同源盒转录因子2(Cdx2)通路干扰炎症反应,如虎杖、木蝴蝶、黄芩、黄连、丹参、白芷、人参、香附、五味子、高良姜等。本文综述了近年来PXR调节炎症反应的最新研究成果以及中药激活PXR干预炎症反应的机制,以期为今后的研究提供参考。 相似文献
4.
5.
The mucosal glycocalyx of the ocular surface constitutes the point of interaction between the tear film and the apical epithelial cells. Membrane-associated mucins (MAMs) are the defining molecules of the glycocalyx in all mucosal epithelia. Long recognized for their biophysical properties of hydration, lubrication, anti-adhesion and repulsion, MAMs maintain the wet ocular surface, lubricate the blink, stabilize the tear film and create a physical barrier to the outside world. However, it is increasingly appreciated that MAMs also function as cell surface receptors that transduce information from the outside to the inside of the cell. A number of excellent review articles have provided perspective on the field as it has progressed since 1987, when molecular cloning of the first MAM was reported. The current article provides an update for the ocular surface, placing it into the broad context of findings made in other organ systems, and including new genes, new protein functions and new biological roles. We discuss the epithelial tissue-equivalent with mucosal differentiation, the key model system making these advances possible. In addition, we make the first systematic comparison of MAMs in human and mouse, establishing the basis for using knockout mice for investigations with the complexity of an in vivo system. Lastly, we discuss findings from human genetics/genomics, which are providing clues to new MAM roles previously unimagined. Taken together, this information allows us to generate hypotheses for the next stage of investigation to expand our knowledge of MAM function in intracellular signaling and roles unique to the ocular surface. 相似文献
6.
7.
《Advances in medical sciences》2020,65(2):386-393
PurposeExaggerated release of proinflammatory mediators during sepsis contributes to inadequate vasodilatation and depressed myocardial contractility, which lead to development of shock and circulatory collapse. The aim of the study was to evaluate the effect of IL-6 and aging on activation of intracellular signaling pathways in the myocardium induced by bacterial lipopolysaccharide (LPS) administration.Material/methodsLPS was injected intraperitoneally to male 3- and 24-month old mice with systemic IL-6 gene knock-out (IL-6KO) and the reference strain (WT). LPS was given intraperitoneally in single low (0.1 mg/kg) or high (10 mg/kg) dose, or in two doses (0.1 + 10 mg/kg) with 24-h delay. The expression and phosphorylation of STAT3, ERK1/2, Akt1/2/3 proteins in the left ventricular myocardium was evaluated after 24 h using Western blotting.ResultsLow LPS dose induced higher STAT3 phosphorylation only in old IL-6KO mice, not affecting ERK1/2 and Akt1/2/3 phosphorylation in any group. High LPS dose upregulated STAT3 phosphorylation similarly in all groups, reduced ERK1/2 expression in young WT mice and upregulated Akt1/2/3 expression and phosphorylation in young IL-6KO mice. Pretreatment with low LPS dose attenuated phosphorylation of STAT3 in both old groups and phosphorylation of Akt1/2/3 in young IL-6KO group. Two-dose approach also significantly potentiated ERK1/2 phosphorylation in both old groups.ConclusionsObtained results show that IL-6 deficiency alters the activity of intracellular signaling pathways: JAK/STAT in old and Akt in young LPS-treated mice. This may indicate that lack of IL-6 attenuates Akt-related cytoprotective effect of pretreatment with low LPS dose in young but not in aged animals. 相似文献
8.
《Drug discovery today》2022,27(8):2373-2385
Autophagy, an evolutionarily highly conserved cellular degradation process, plays the Janus role (either cytoprotective or death-promoting) in colorectal cancer, so the targeting of several key autophagic pathways with small-molecule compounds may be a new therapeutic strategy. In this review, we discuss autophagy-associated cell death pathways and key cytoprotective autophagy pathways in colorectal cancer. Moreover, we summarize a series of small-molecule compounds that have the potential to modulate autophagy-associated cell death or cytoprotective autophagy for therapeutic purposes. Taken together, these findings demonstrate the Janus role of autophagy in colorectal cancer, and shed new light on the exploitation of a growing number of small-molecule compounds to target autophagy in future cancer drug discovery. 相似文献
9.
Ruchuon Yokchom Somsak Laiwejpithaya Weerakanya Maneeprakorn Satita Tapaneeyakorn Jundee Rabablert Tararaj Dharakul 《Nanomedicine : nanotechnology, biology, and medicine》2018,14(3):1051-1058
The aim of this study was to develop a paper-based immunosensor for cervical cancer screening, with signal amplification by multifunctionalized gold nanoparticles (AuNPs). The AuNPs were functionalized with a highly specific antibody to the p16INK4a cancer biomarker. The signal was amplified using a combination of the peroxidase activity of horseradish peroxidase (HRP) enzyme-antibody conjugate and the peroxidase-like activity of the AuNPs. The immune complex of p16INK4a protein and multifunctionalized AuNPs was deposited on the nitrocellulose membrane, and a positive result was generated by catalytic oxidation of peroxidase enzyme substrate 3,3’,5,5’-Tetramethylbenzidine (TMB). The entire reaction occurred on the membrane within 30 min. Evaluation in clinical samples revealed 85.2% accuracy with a kappa coefficient of 0.69. This proof of concept study demonstrates the successful development of a highly accurate, paper-based immunosensor that is easy to interpret using the naked eye and that is suitable for cervical cancer screening in low-resource settings. 相似文献
10.
Céline Anquetil Olivier Boyer Nadège Wesner Olivier Benveniste Yves Allenbach 《Autoimmunity reviews》2019,18(3):223-230
Over the past few years, myositis-specific autoantibodies played an increasing role in the inflammatory idiopathic myositis definition. They became the critical immunological marker for immune-mediated necrotizing myopathy diagnosis (IMNM) since the paradigm switch from histological to serological criteria.This review is focused on the key role of the anti-signal recognition particle (anti-SRP) and the anti-3-Hydroxy-3-MethylGlutaryl-Coenzyme A Reductase (anti-HMGCR) antibodies in immune-mediated necrotizing myopathy.Anti-SRP and anti-HMGCR antibodies are robust diagnostic tools in case of both the classical subacute form and the slowly progressive form of IMNM that may mimic muscular dystrophy. Anti-SRP and anti-HMGCR patients share clinical, biological and histological features with some antibody-associated specificity. Anti-SRP patients harbour more severe muscle weakness and atrophy with severe muscle damage on magnetic resonance imaging study. Approximately 10–20% of anti-SRP patients develop extramuscular symptoms, especially lung interstitial disease. Conversely, anti-HMGCR patients are often associated with statin exposure. In both cases, patients have a poor outcome with frequent relapse and the use of combined immunotherapy. Of note, various data suggest a direct pathogenic role of these antibodies reinforcing the interest in targeted therapeutic strategy. 相似文献