全文获取类型
收费全文 | 17900篇 |
免费 | 1365篇 |
国内免费 | 847篇 |
专业分类
耳鼻咽喉 | 103篇 |
儿科学 | 127篇 |
妇产科学 | 203篇 |
基础医学 | 2603篇 |
口腔科学 | 394篇 |
临床医学 | 1421篇 |
内科学 | 2432篇 |
皮肤病学 | 242篇 |
神经病学 | 977篇 |
特种医学 | 722篇 |
外国民族医学 | 6篇 |
外科学 | 896篇 |
综合类 | 2576篇 |
现状与发展 | 5篇 |
一般理论 | 3篇 |
预防医学 | 1692篇 |
眼科学 | 553篇 |
药学 | 2620篇 |
6篇 | |
中国医学 | 1438篇 |
肿瘤学 | 1093篇 |
出版年
2024年 | 30篇 |
2023年 | 207篇 |
2022年 | 269篇 |
2021年 | 635篇 |
2020年 | 520篇 |
2019年 | 483篇 |
2018年 | 466篇 |
2017年 | 526篇 |
2016年 | 538篇 |
2015年 | 680篇 |
2014年 | 1086篇 |
2013年 | 1359篇 |
2012年 | 1079篇 |
2011年 | 1199篇 |
2010年 | 949篇 |
2009年 | 931篇 |
2008年 | 1023篇 |
2007年 | 911篇 |
2006年 | 858篇 |
2005年 | 782篇 |
2004年 | 715篇 |
2003年 | 621篇 |
2002年 | 580篇 |
2001年 | 500篇 |
2000年 | 366篇 |
1999年 | 338篇 |
1998年 | 328篇 |
1997年 | 290篇 |
1996年 | 263篇 |
1995年 | 213篇 |
1994年 | 164篇 |
1993年 | 163篇 |
1992年 | 135篇 |
1991年 | 96篇 |
1990年 | 98篇 |
1989年 | 93篇 |
1988年 | 62篇 |
1987年 | 66篇 |
1986年 | 60篇 |
1985年 | 81篇 |
1984年 | 79篇 |
1983年 | 55篇 |
1982年 | 41篇 |
1981年 | 41篇 |
1980年 | 39篇 |
1979年 | 31篇 |
1978年 | 15篇 |
1977年 | 16篇 |
1976年 | 19篇 |
1973年 | 4篇 |
排序方式: 共有10000条查询结果,搜索用时 328 毫秒
1.
《Saudi Pharmaceutical Journal》2022,30(11):1572-1588
Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of a metabolic syndrome caused by excessive accumulation of fat in the liver. Orthosiphon stamineus also known as Orthosiphon aristatus is a medicinal plant with possible potential beneficial effects on various metabolic disorders. This study aims to investigate the in vitro inhibitory effects of O. stamineus on hepatic fat accumulation and to further use the computational systems pharmacology approach to identify the pharmacokinetic properties of the bioactive compounds of O. stamineus and to predict their molecular mechanisms against NAFLD. Methods: The effects of an ethanolic extract of O. stamineus leaves on cytotoxicity, fat accumulation and antioxidant activity were assessed using HepG2 cells. The bioactive compounds of O. stamineus were identified using LC/MS and two bioinformatics databases, namely the Traditional Chinese Medicine Integrated Database (TCMID) and the Bioinformatics Analysis Tool for the Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Pathway enrichment analysis was performed on the predicted targets of the bioactive compounds to provide a systematic overview of the molecular mechanism of action, while molecular docking was used to validate the predicted targets. Results: A total of 27 bioactive compounds corresponding to 50 potential NAFLD-related targets were identified. O. stamineus exerts its anti-NAFLD effects by modulating a variety of cellular processes, including oxidative stress, mitochondrial β-oxidation, inflammatory signalling pathways, insulin signalling, and fatty acid homeostasis pathways. O. stamineus is significantly targeting many oxidative stress regulators, including JNK, mammalian target of rapamycin (mTOR), NFKB1, PPAR, and AKT1. Molecular docking analysis confirmed the expected high affinity for the potential targets, while the in vitro assay indicates the ability of O. stamineus to inhibit hepatic fat accumulation. Conclusion: Using the computational systems pharmacology approach, the potentially beneficial effect of O. stamineus in NAFLD was indicated through the combination of multiple compounds, multiple targets, and multicellular components. 相似文献
2.
Osric A. Forrest Daniel M. Chopyk Yael Gernez Milton R. Brown Carol K. Conrad Richard B. Moss Vin Tangpricha Limin Peng Rabindra Tirouvanziam 《Journal of cystic fibrosis》2019,18(1):64-70
Background
Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.Methods
Resistin levels were measured in plasma and sputum from three retrospective CF cohorts spanning a wide range of disease. We also assessed the ability of neutrophils to secrete resistin upon activation in vitro. Finally, we constructed a multivariate model assessing the relationship between resistin levels and lung function.Results
Plasma resistin levels were only marginally higher in CF than in healthy control subjects. By contrast, sputum resistin levels were very high in CF, reaching 50–100 fold higher levels than in plasma. Among CF patients, higher plasma resistin levels were associated with allergic bronchopulmonary aspergillosis, and higher sputum resistin levels were associated with CF-related diabetes. Mechanistically, in vitro release of neutrophil primary granules was concomitant with resistin secretion. Overall, sputum resistin levels were negatively correlated with CF lung function, independently of other variables (age, sex, and genotype).Conclusions
Our data establish relationships between resistin levels in the plasma and sputum of CF patients that correlate with disease status, and identify resistin as a novel mechanistic link between neutrophilic inflammation and lung disease in CF. 相似文献3.
《The Journal of arthroplasty》2022,37(10):1945-1950
The results of statistical tests in orthopedic studies are typically reported using P-values. If a P-value is smaller than the pre-determined level of significance (eg, < .05), the null hypothesis is rejected in support of the alternative. This automaticity in interpreting statistical results without consideration of the power of the study has been denounced over the years by statisticians, since it can potentially lead to misinterpretation of the study conclusions. In this paper, we review fundamental misconceptions and misinterpretations of P-values and power, along with their connection with confidence intervals, and we provide guidelines to orthopedic researchers for evaluating and reporting study results. We provide real-world orthopedic examples to illustrate the main concepts. Please visit the following https://youtu.be/bdPU4luYmF0 for videos that explain the highlights of the paper in practical terms. 相似文献
4.
《Drug discovery today》2022,27(6):1733-1742
Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action. 相似文献
5.
6.
目的:通过检测人绒癌细胞株Be Wo合体化过程中增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)、生存素(Survivin)蛋白表达的变化,探讨滋养细胞合体化后增殖性的变化,为恶性滋养细胞肿瘤,尤其是耐药恶性滋养细胞肿瘤的临床治疗提供新的思路和方法。方法:利用毛喉素(forskolin)诱导Be Wo细胞株融合;应用逆转录聚合酶链反应(RT-PCR)检测促融素(Syncytin)在forskolin作用不同时间的Be Wo细胞株中的表达;应用蛋白质印迹(Western blotting)检测PCNA、Survivin蛋白在forskolin作用不同时间的Be Wo细胞株中的表达;应用噻唑蓝比色分析实验(MTT)法检测forskolin作用不同时间的绒癌细胞株Be Wo的增殖能力。结果:1forskolin作用后的Be Wo细胞株Syncytin基因的表达增强,且随着forskolin作用时间的延长,Syncytin的表达更强,于48 h达到高峰。2forskolin作用后的Be Wo细胞株PCNA、Survivin蛋白的表达降低。3forskolin作用后的Be Wo细胞株的增殖能力下降,且不同作用时间的差异有统计学意义;forskolin作用的时间越长,Be Wo细胞株增殖能力下降越明显。结论:人绒癌细胞株Be Wo合体化后PCNA、Survivin蛋白的表达降低,说明人绒癌细胞株Be Wo合体化后增殖性降低,推测诱导滋养细胞合体化可能对临床治疗恶性滋养细胞肿瘤具有一定作用。 相似文献
7.
When living organisms become sick as a result of a bacterial infection, a suite of brain-mediated responses occur, including fever, anorexia and sleepiness. Systemic administration of lipopolysaccharide (LPS), a common constituent of bacterial cell walls, increases body temperature and non-rapid eye movement (NREM) sleep in animals and induces the production of pro-inflammatory prostaglandins (PGs). PGE2 is the principal mediator of fever, and both PGE2 and PGD2 regulate sleep–wake behavior. The extent to which PGE2 and PGD2 are involved in the effect of LPS on NREM sleep remains to be clarified. Therefore, we examined LPS-induced changes in body temperature and NREM sleep in mice with nervous system-specific knockouts (KO) for the PGE2 receptors type EP3 or EP4, in mice with total body KO of microsomal PGE synthase-1 or the PGD2 receptor type DP, and in mice treated with the cyclooxygenase (COX) inhibitor meloxicam. We observed that LPS-induced NREM sleep was slightly attenuated in mice lacking EP4 receptors in the nervous system, but was not affected in any of the other KO mice or in mice pretreated with the COX inhibitor. These results suggest that the effect of LPS on NREM sleep is partially dependent on PGs and is likely mediated mainly by other pro-inflammatory substances. In addition, our data show that the main effect of LPS on body temperature is hypothermia in the absence of nervous system EP3 receptors or in the presence of a COX inhibitor. 相似文献
8.
目的:采用核磁共振氢谱(~1H-NMR)植物代谢组学技术比较青海产区枸杞子与其他产区(宁夏、甘肃、新疆、内蒙古)枸杞子的化学成分差异。方法:收集5个产区共97份枸杞子样本,其中青海61个样本,采用50%甲醇提取,检测~1H-NMR图谱,结合多元统计分析,对比青海产区枸杞子与其他产区枸杞子的化学差异性,并对各产区样本的枸杞多糖进行含量测定(以无水葡萄糖计),检测波长490 nm。结果:枸杞子的~1H-NMR图谱共检测到32个化学成分,多元统计分析表明青海产区枸杞子与其他产区样本相比,无明显分离趋势;青海产区枸杞子与宁夏产区相比,以及青海省6个不同地区的枸杞子相比,重叠样品较多,均不能显著分开。相似度结果表明,大多数样品的相似度0.85;化合物的单变量分析结果显示,除了蔗糖、葡萄糖、脯氨酸等个别代谢物在各产区样本中存在显著差异外,其余代谢物在各产区样品中的含量分布基本一致。青海与其他产区样本中枸杞多糖含量无显著性差异,且枸杞多糖含量与~1H-NMR指认的小分子化合物的相关系数处于-0.2~0.4。结论:采用~1HNMR植物代谢组学技术从整体化学组成上分析了青海产区枸杞子的化学特征,并结合枸杞多糖含量测定,显示青海产区枸杞子与其他产区枸杞子的化学差异较小。建立的基于~1H-NMR的枸杞子质量评价方法可为其质控水平提升及种植产区选择提供科学依据。 相似文献
9.
目的 总结脑血管疾病后Holmes震颤的临床、影像和电生理特点。
方法 回顾性分析2015年8月-2019年8月就诊于首都医科大学附属北京天坛医院的4例脑血管疾病
所致Holmes震颤患者,对其临床、影像及电生理资料进行分析总结。
结果 4例患者中2例由高血压性脑出血引起,另外2例分别由脑动静脉畸形和脑海绵状血管瘤破裂
出血引起。Holmes震颤出现于原发病后1~24个月,表现为病灶对侧肢体震颤,以上肢多见。头颅MRI
检查显示2例患者病灶仅累及丘脑,2例同时累及丘脑和中脑。震颤分析显示静止、姿势、意向及持物
1000 g几种状态下震颤的峰频率均在2.6~3.8 Hz,意向状态震颤半宽功率高于静止状态。主动肌与
拮抗肌在静息时以同步收缩为主,姿势、意向和持物时以交替收缩为主。3例接受普拉克索治疗均有
不同程度缓解。
结论 Holmes震颤多由累及中脑、丘脑部位脑血管疾病引起,表现为2~4 Hz低频震颤,意向状态震
颤明显,部分患者多巴胺受体激动剂治疗有效。 相似文献
10.