全文获取类型
收费全文 | 2031篇 |
免费 | 180篇 |
国内免费 | 215篇 |
专业分类
儿科学 | 23篇 |
妇产科学 | 30篇 |
基础医学 | 182篇 |
临床医学 | 80篇 |
内科学 | 138篇 |
皮肤病学 | 1篇 |
神经病学 | 1042篇 |
特种医学 | 10篇 |
外科学 | 53篇 |
综合类 | 136篇 |
预防医学 | 22篇 |
眼科学 | 159篇 |
药学 | 417篇 |
1篇 | |
中国医学 | 122篇 |
肿瘤学 | 10篇 |
出版年
2024年 | 5篇 |
2023年 | 29篇 |
2022年 | 23篇 |
2021年 | 79篇 |
2020年 | 82篇 |
2019年 | 65篇 |
2018年 | 70篇 |
2017年 | 88篇 |
2016年 | 79篇 |
2015年 | 98篇 |
2014年 | 130篇 |
2013年 | 250篇 |
2012年 | 129篇 |
2011年 | 162篇 |
2010年 | 163篇 |
2009年 | 140篇 |
2008年 | 138篇 |
2007年 | 129篇 |
2006年 | 127篇 |
2005年 | 86篇 |
2004年 | 75篇 |
2003年 | 61篇 |
2002年 | 70篇 |
2001年 | 36篇 |
2000年 | 24篇 |
1999年 | 17篇 |
1998年 | 19篇 |
1997年 | 13篇 |
1996年 | 11篇 |
1995年 | 10篇 |
1994年 | 7篇 |
1993年 | 6篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1990年 | 1篇 |
排序方式: 共有2426条查询结果,搜索用时 234 毫秒
1.
Zi-Qi Shao Shan-Shan Dou Jun-Ge Zhu Hui-Qing Wang Chun-Mei Wang Bao-Hua Cheng Bo Bai 《中国神经再生研究》2021,16(6):1044
Apelin-13 is a novel endogenous ligand for an angiotensin-like orphan G-protein coupled receptor, and it may be neuroprotective against cerebral ischemia injury. However, the precise mechanisms of the effects of apelin-13 remain to be elucidated. To investigate the effects of apelin-13 on apoptosis and autophagy in models of cerebral ischemia/reperfusion injury, a rat model was established by middle cerebral artery occlusion. Apelin-13(50 μg/kg) was injected into the right ventricle as a treatment. In addition, an SH-SY5 Y cell model was established by oxygen-glucose deprivation/reperfusion, with cells first cultured in sugar-free medium with 95% N2 and 5% CO2 for 4 hours and then cultured in a normal environment with sugar-containing medium for 5 hours. This SH-SY5 Y cell model was treated with 10–7 M apelin-13 for 5 hours. Results showed that apelin-13 protected against cerebral ischemia/reperfusion injury. Apelin-13 treatment alleviated neuronal apoptosis by increasing the ratio of Bcl-2/Bax and significantly decreasing cleaved caspase-3 expression. In addition, apelin-13 significantly inhibited excessive autophagy by regulating the expression of LC3 B, p62, and Beclin1. Furthermore, the expression of Bcl-2 and the phosphatidylinositol-3-kinase(PI3 K)/Akt/mammalian target of rapamycin(mTOR) pathway was markedly increased. Both LY294002(20 μM) and rapamycin(500 nM), which are inhibitors of the PI3 K/Akt/mTOR pathway, significantly attenuated the inhibition of autophagy and apoptosis caused by apelin-13. In conclusion, the findings of the present study suggest that Bcl-2 upregulation and mTOR signaling pathway activation lead to the inhibition of apoptosis and excessive autophagy. These effects are involved in apelin-13-induced neuroprotection against cerebral ischemia/reperfusion injury, both in vivo and in vitro. The study was approved by the Animal Ethical and Welfare Committee of Jining Medical University, China(approval No. 2018-JS-001) in February 2018. 相似文献
2.
3.
Apoptosis is an important factor during the early stage of intracerebral hemorrhage.MiR-181 c plays a key regulatory role in apoptosis.However,whether miR-181 c is involved in apoptosis of prophase cells after intracerebral hemorrhage remains unclear.Therefore,in vitro and in vivo experiments were conducted to test this hypothesis.In vivo experiments:collagenase type VII was injected into the basal ganglia of adult Sprague-Dawley rats to establish an intracerebral hemorrhage model.MiR-181 c mimic or inhibitor was injected in situ 4 hours after intracerebral hemorrhage.Neurological functional defects(neurological severity scores)were assessed 1,7,and 14 days after model establishment.Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and western blot assay were conducted 14 days after model establishment.In vitro experiments:PC12 cells were cultured under oxygen-glucose deprivation,and hemins were added to simulate intracerebral hemorrhage in vitro.MiR-181 c mimic or inhibitor was added to regulate miR-181 c expression.3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,luciferase reporter system,and western blot assay were performed.Experimental results revealed differences in miR-181 c expression in brain tissues of both patients and rats with cerebral hemorrhage.In addition,in vitro experiments found that miR-181 c overexpression could upregulate the Bcl-2/Bax ratio to inhibit apoptosis,while inhibition of miR-181 c expression could reduce the Bcl-2/Bax ratio and aggravate apoptosis of cells.Regulation of apoptosis occurred through the phosphoinositide 3 kinase(PI3 K)/Akt pathway by targeting of phosphatase and tensin homolog deleted on chromosome ten(PTEN).Higher miR-181 c overexpression correlated with lower neurological severity scores,indicating better recovery of neurological function.In conclusion,miR-181 c affects the prognosis of intracerebral hemorrhage by regulating apoptosis,and these effects might be directly mediated and regulated by targeting of the PTEN\PI3 K/Akt pathway and Bcl-2/Bax ratio.Furthermore,these results indicated that miR-181 c played a neuroprotective role in intracerebral hemorrhage by regulating apoptosis of nerve cells,thus providing a potential target for the prevention and treatment of intracerebral hemorrhage.Testing of human serum was authorized by the Ethics Committee of China Medical University(No.2012-38-1)on February 20,2012.The protocol was registered with the Chinese Clinical Trial Registry(Registration No.ChiCTR-COC-17013559).The animal study was approved by the Institutional Animal Care and Use Committee of China Medical University(approval No.2017008)on March 8,2017. 相似文献
4.
5.
Multiple sclerosis(MS)is an inflammatory demyelinating disease of the central nervous system.The disability caused by inflammatory demyelination clinically dominates the early stages of relapsing-remitting MS and is reversible.Once there is considerable loss of axons,MS patients enter a secondary progressive stage.Disease-modifying drugs currently in use for MS suppress the immune system and reduce relapse rates but are not effective in the progressive stage.Various animal models of MS(mostly mouse and rat)have been established and proved useful in studying the disease process and response to therapy.The experimental autoimmune encephalomyelitis animal studies reviewed here showed that a chronic progressive disease can be induced by immunization with appropriate amounts of myelin oligodendrocyte glycoprotein together with mycobacterium tuberculosis and pertussis toxin in Freund's adjuvant.The clinical manifestations of autoimmune encephalomyelitis disease were prevented or reduced by treatment with certain pharmacological agents given prior to,at,or after peak disease,and the agents had protective effects as shown by inhibiting demyelination and damage to neurons,axons and oligodendrocytes.In the cuprizone-induced toxicity animal studies,the pharmacological agents tested were able to promote remyelination and increase the number of oligodendrocytes when administered therapeutically or prophylactically.A monoclonal IgM antibody protected axons in the spinal cord and preserved motor function in animals inoculated with Theiler's murine encephalomyelitis virus.In all these studies the pharmacological agents were administered singly.A combination therapy may be more effective,especially using agents that target neuroinflammation and neurodegeneration,as they may exert synergistic actions. 相似文献
6.
Melatonin enhances L‐DOPA therapeutic effects,helps to reduce its dose,and protects dopaminergic neurons in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐induced parkinsonism in mice 下载免费PDF全文
Amit Naskar Debashis Dutta Kochupurackal P. Mohanakumar 《Journal of pineal research》2015,58(3):262-274
L‐3,4‐dihydroxyphenylalanine (L‐DOPA) reduces symptoms of Parkinson's disease (PD), but suffers from serious side effects on long‐term use. Melatonin (10–30 mg/kg, 6 doses at 10 hr intervals) was investigated to potentiate L‐DOPA therapeutic effects in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced parkinsonism in mice. Striatal tyrosine hydroxylase (TH) immunoreactivity, TH, and phosphorylated ser 40 TH (p‐TH) protein levels were assayed on 7th day. Nigral TH‐positive neurons stereology was conducted on serial sections 2.8 mm from bregma rostrally to 3.74 mm caudally. MPTP caused 39% and 58% decrease, respectively, in striatal fibers and TH protein levels, but 2.5‐fold increase in p‐TH levels. About 35% TH neurons were lost between 360 and 600 μm from 940 μm of the entire nigra analyzed, but no neurons were lost between 250 μm rostrally and 220 μm caudally. When L‐DOPA in small doses (5–8 mg/kg) failed to affect MPTP‐induced akinesia or catalepsy, co‐administration of melatonin with L‐DOPA attenuated these behaviors. Melatonin administration significantly attenuated MPTP‐induced loss in striatal TH fibers (82%), TH (62%) and p‐TH protein (100%) levels, and nigral neurons (87–100%). Melatonin failed to attenuate MPTP‐induced striatal dopamine depletion. L‐DOPA administration (5 mg/kg, once 40 min prior to sacrifice, p.o.) in MPTP‐ and melatonin‐treated mice caused significant increase in striatal dopamine (31%), as compared to L‐DOPA and MPTP‐treated mice. This was equivalent to 8 mg/kg L‐DOPA administration in parkinsonian mouse. Therefore, prolonged, effective use of L‐DOPA in PD with lesser side effects could be achieved by treating with 60% lower doses of L‐DOPA along with melatonin. 相似文献
7.
目的?研究桂枝中酚类提取物木脂素的潜在作用靶点。方法?在药效团模型数据库中筛选出与木脂素衍生物匹配值(FitValue)大于0.75的药效团模型;运用反向对接技术,从上述药效团模型所对应的靶点蛋白中挑选出与木脂素衍生物结合能最低的蛋白;以该靶蛋白已报道的抑制剂建立3D-QSAR药效团模型预测木脂素衍生物的活性,同时通过荧光偏振实验测试化合物1与Tankyrase 1蛋白的结合力,通过Western blot实验测试加入化合物1后细胞中Tankyrase 1蛋白的含量变化;最后用分子动力学模拟分析木脂素衍生物与该蛋白的作用模式。结果?与木脂素衍生物匹配值大于0.75的药效团模型有17个,其中4个为神经保护类靶点,占比(24%)最大;反向对接结果显示该化合物与Tankyrase 1蛋白(PDB ID:4TOR)的结合能(E=-66?kcal/mol)最低;预测该化合物的活性为0.61?μmol/L,荧光偏振实验测得化合物1与Tankyrase 1蛋白的结合力Ki=(0.15±0.01)μmol/L,属于中等抑制,Western blot表明在SW480细胞中化合物1使Tankyrase 1蛋白的表达下降;且分子动力学结果显示对接构象与该靶点已报道的抑制剂类似。结论?经过对桂枝中酚类提取物木脂素衍生物的反向找靶,以及活性测试确定其对Tankyrase 1蛋白具有潜在的抑制活性。 相似文献
8.
Bo Zhen Jia-Wen Hu Jia-Jia Wang Meng-Jiao Shi Li Li 《Journal of Asian natural products research》2019,21(5):409-418
Seven natural compounds, including new compounds hyperascyrins L-N (1-3) and four known compounds (4-7), were acquired from the aerial parts of Hypericum ascyron, that were all identified as methylated polycyclic polyprenylated acylphloroglucinol derivatives (mPPAPs). The structures of these compounds were established by NMR spectroscopy, experimental and calculated electronic circular dichroism (ECD) data. The neuroprotective activities and hepatoprotective activity of these compounds (10 µM) were evaluated. Compounds 1, 2 and 3 exhibited neuroprotection activity. Compounds 1 and 3 show hepatoprotective activity. 相似文献
9.
10.