全文获取类型
收费全文 | 10826篇 |
免费 | 1835篇 |
国内免费 | 569篇 |
专业分类
耳鼻咽喉 | 63篇 |
儿科学 | 115篇 |
妇产科学 | 113篇 |
基础医学 | 2374篇 |
口腔科学 | 262篇 |
临床医学 | 767篇 |
内科学 | 1894篇 |
皮肤病学 | 108篇 |
神经病学 | 1299篇 |
特种医学 | 120篇 |
外国民族医学 | 2篇 |
外科学 | 783篇 |
综合类 | 1167篇 |
现状与发展 | 4篇 |
预防医学 | 293篇 |
眼科学 | 181篇 |
药学 | 1355篇 |
3篇 | |
中国医学 | 854篇 |
肿瘤学 | 1473篇 |
出版年
2024年 | 51篇 |
2023年 | 420篇 |
2022年 | 604篇 |
2021年 | 1012篇 |
2020年 | 812篇 |
2019年 | 637篇 |
2018年 | 615篇 |
2017年 | 573篇 |
2016年 | 673篇 |
2015年 | 753篇 |
2014年 | 902篇 |
2013年 | 987篇 |
2012年 | 647篇 |
2011年 | 632篇 |
2010年 | 504篇 |
2009年 | 515篇 |
2008年 | 494篇 |
2007年 | 375篇 |
2006年 | 301篇 |
2005年 | 253篇 |
2004年 | 212篇 |
2003年 | 162篇 |
2002年 | 103篇 |
2001年 | 98篇 |
2000年 | 61篇 |
1999年 | 76篇 |
1998年 | 51篇 |
1997年 | 39篇 |
1996年 | 44篇 |
1995年 | 52篇 |
1994年 | 46篇 |
1993年 | 39篇 |
1992年 | 40篇 |
1991年 | 31篇 |
1990年 | 35篇 |
1989年 | 34篇 |
1988年 | 37篇 |
1987年 | 24篇 |
1986年 | 22篇 |
1985年 | 44篇 |
1984年 | 61篇 |
1983年 | 36篇 |
1982年 | 45篇 |
1981年 | 19篇 |
1980年 | 14篇 |
1979年 | 8篇 |
1978年 | 6篇 |
1977年 | 10篇 |
1976年 | 8篇 |
1975年 | 5篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
41.
42.
《Journal of thoracic oncology》2020,15(1):62-79
IntroductionMounting evidence supports a role for estrogen signaling in NSCLC progression. We previously reported a seven-gene signature that predicts prognosis in estrogen receptor β positive (ERβ+) NSCLC. The signature defines a network comprised of ER and human EGFR-2/3 (HER2/HER3) signaling.MethodsWe tested the efficacy of combining the pan-HER inhibitor, dacomitinib, with the estrogen antagonist, fulvestrant, in ERβ+ NSCLC models with differing genotypes. We assessed the potency of this combination on xenograft growth and survival of host mice, and the ability to reverse the gene signature associated with poor outcome.ResultsSynergy was observed between dacomitinib and fulvestrant in three human ERβ+ NSCLC models: 201T (wild-type EGFR), A549 (KRAS mutant), and HCC827 (EGFR 19 deletion) with combination indices of 0.1-0.6. The combination, but not single agents, completely reversed the gene signature associated with poor prognosis in a mechanism that is largely mediated by activator protein 1 downregulation. In vivo, the combination also induced tumor regression and reversed the gene signature. In HCC827 xenografts treated with the combination, survival of mice was prolonged after therapy discontinuation, tumors that recurred were less aggressive, and two mechanisms of HER inhibitor resistance involving c-Met activation and PTEN loss were blocked.ConclusionsThe combination of an ER blocker and a pan-HER inhibitor provides synergistic efficacy in different models of ERβ+ NSCLC. Our data support the use of this combination clinically, considering its ability to induce potent antitumor effects and produce a gene signature that predicts better clinical outcomes. 相似文献
43.
Gambogic acid (GA), the major active ingredient of gamboge, has been approved by the Chinese Food and Drug Administration for clinical trials in cancer patients due to its strong anticancer activity. However, our previous research showed that GA was teratogenic against zebrafish fin development. To explore the teratogenicity and the underlying mechanisms, zebrafish (Danio rerio) embryos were used. The morphological observations revealed that GA caused fin defects in zebrafish embryos in a concentration-dependent manner. The critical exposure time of GA to reveal teratogenicity was before 8 hpf (hours post fertilization). LC/MS/MS analysis revealed that a maximum bioconcentration of GA was occurred at 4 hpf. Q-PCR data showed that GA treatment resulted in significant inactivation of RA signaling which could be partially rescued by the exogenous supply of RA. These results indicate the potential teratogenicity of GA and provide evidence for a caution in its future clinic use. 相似文献
44.
Reduced silent information regulator 1 signaling exacerbates myocardial ischemia–reperfusion injury in type 2 diabetic rats and the protective effect of melatonin 下载免费PDF全文
Guolong Zhao Zhenxiao Jin Mengen Zhai Yang Yang Wensheng Chen Jincheng Liu Wei Yi Jian Yang Dinghua Yi Weixun Duan Shiqiang Yu 《Journal of pineal research》2015,59(3):376-390
Diabetes mellitus (DM) increases myocardial oxidative stress and endoplasmic reticulum (ER) stress. Melatonin confers cardioprotective effect by suppressing oxidative damage. However, the effect and mechanism of melatonin on myocardial ischemia–reperfusion (MI/R) injury in type 2 diabetic state are still unknown. In this study, we developed high‐fat diet‐fed streptozotocin (HFD‐STZ) rat, a well‐known type 2 diabetic model, to evaluate the effect of melatonin on MI/R injury with a focus on silent information regulator 1 (SIRT1) signaling, oxidative stress, and PERK/eIF2α/ATF4‐mediated ER stress. HFD‐STZ treated rats were exposed to melatonin treatment in the presence or the absence of sirtinol (a SIRT1 inhibitor) and subjected to MI/R surgery. Compared with nondiabetic animals, type 2 diabetic rats exhibited significantly decreased myocardial SIRT1 signaling, increased apoptosis, enhanced oxidative stress, and ER stress. Additionally, further reduced SIRT1 signaling, aggravated oxidative damage, and ER stress were found in diabetic animals subjected to MI/R surgery. Melatonin markedly reduced MI/R injury by improving cardiac functional recovery and decreasing myocardial apoptosis in type 2 diabetic animals. Melatonin treatment up‐regulated SIRT1 expression, reduced oxidative damage, and suppressed PERK/eIF2α/ATF4 signaling. However, these effects were all attenuated by SIRT1 inhibition. Melatonin also protected high glucose/high fat cultured H9C2 cardiomyocytes against simulated ischemia–reperfusion injury‐induced ER stress by activating SIRT1 signaling while SIRT1 siRNA blunted this action. Taken together, our study demonstrates that reduced cardiac SIRT1 signaling in type 2 diabetic state aggravates MI/R injury. Melatonin ameliorates reperfusion‐induced oxidative stress and ER stress via activation of SIRT1 signaling, thus reducing MI/R damage and improving cardiac function. 相似文献
45.
Exploring the transition experiences of students entering into preregistration nursing degree programs with previous professional nursing qualifications: an integrative review 下载免费PDF全文
Marion Tower PhD RN Marie Cooke PhD RN Bernadette Watson RN BN Nick Buys PhD Keithia Wilson PhD 《Journal of clinical nursing》2015,24(9-10):1174-1188
46.
47.
目的:应用条件性重编程细胞(conditionally reprogrammed cells,CRCs)技术建立人肺癌细胞体外长期培养体系,研究扁塑藤素对人肺癌CRCs增殖和迁移能力的影响,并探讨相关作用机制。方法:免疫组化法检测Notch 1、HES1和Cyclin D3在肿瘤组织和癌旁组织中的表达水平;使用CRCs技术分离培养非小细胞肺癌原代细胞;使用2,4,8,16 μmol·L-1的扁塑藤素处理人肺癌CRCs,MTS法检测细胞活力,Annexin V/PI流式细胞术检测细胞凋亡,Transwell法检测细胞迁移能力,Western Blot检测细胞中Notch信号通路相关蛋白Notch 1、HES1和Cyclin D3的表达水平。结果:在非小细胞肺癌患者肿瘤组织中Notch 1、HES1和Cyclin D3的表达水平高于癌旁组织;扁塑藤素能够诱导人肺癌CRCs死亡,并在一定范围内呈现时间和浓度依赖性(P<0.05);随着扁塑藤素作用浓度的增高,人肺癌CRCs凋亡率明显增高(P<0.05),细胞迁移能力下降(P<0.05);扁塑藤素能够下调人肺癌CRCs中Notch 1、HES1和Cyclin D3的蛋白表达水平。结论:扁塑藤素可能通过调控Notch信号通路相关蛋白的表达水平,抑制人肺癌CRCs的增殖和迁移,并诱导其凋亡,为肺癌的治疗提供新的实验数据和理论依据。 相似文献
48.
Nikolet Pavlova 《Expert opinion on therapeutic targets》2019,23(7):631-643
Objectives: A constantly growing number of antibiotic-resistant strains of human pathogenic bacteria is an acute problem. Prolonged illnesses and increasing mortality worldwide mean that there is an urgent need to develop novel antibacterial drugs based on new targets and mechanisms of action. We present in silico analyses of bacterial riboswitches that may be suitable as antibacterial drug targets.Methods: Most bacterial riboswitches are allosteric cis-acting gene control elements located in the 5?-untranslated region of messenger RNAs. Riboswitches sense specific metabolites and regulate the synthesis of some essential cellular metabolites in many pathogenic bacteria but are not found in humans. We present a complete and comprehensive genome-wide bioinformatics analyses of the suitability of eight riboswitches as antibacterial drug targets in various pathogenic bacteria.Results: Based on our in silico analyses, we classify the riboswitches in four different groups based on their suitability to be used as antibacterial drug targets. We have estimated that FMN, SAM-I, glmS, TPP, and Lysine riboswitches are promising targets for antibacterial drug discovery.Conclusion: This research enables us to focus antibacterial drug discovery research only on those riboswitches whose inhibition will result in suppression of the growth of certain pathogenic bacteria. 相似文献
49.
50.