全文获取类型
收费全文 | 1492篇 |
免费 | 385篇 |
国内免费 | 22篇 |
出版年
2024年 | 13篇 |
2023年 | 51篇 |
2022年 | 71篇 |
2021年 | 103篇 |
2020年 | 105篇 |
2019年 | 88篇 |
2018年 | 77篇 |
2017年 | 65篇 |
2016年 | 80篇 |
2015年 | 101篇 |
2014年 | 148篇 |
2013年 | 123篇 |
2012年 | 108篇 |
2011年 | 113篇 |
2010年 | 64篇 |
2009年 | 52篇 |
2008年 | 62篇 |
2007年 | 59篇 |
2006年 | 60篇 |
2005年 | 47篇 |
2004年 | 37篇 |
2003年 | 32篇 |
2002年 | 30篇 |
2001年 | 16篇 |
2000年 | 17篇 |
1999年 | 12篇 |
1998年 | 8篇 |
1997年 | 16篇 |
1996年 | 5篇 |
1995年 | 18篇 |
1994年 | 20篇 |
1993年 | 9篇 |
1992年 | 13篇 |
1991年 | 14篇 |
1990年 | 9篇 |
1989年 | 14篇 |
1988年 | 7篇 |
1987年 | 2篇 |
1986年 | 8篇 |
1985年 | 2篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1976年 | 1篇 |
排序方式: 共有1899条查询结果,搜索用时 15 毫秒
991.
为了探讨转化生长因子(TGF-β1)、外周血纤维化蛋白(FBRS)表达水平变化与肝纤维化发生发展的相关性,本研究选取自2015年5月至2017年6月间在我院诊治的慢性病毒性肝炎患者120例,设为肝炎组。采用免疫组化法检测肝组织TGF-β1的表达水平,酶联免疫分析检测血清中TGF-β1的含量,RT-PCR检测外周血单个核细胞FBRS mRNA的表达水平,分析TGF-β1、FBRS与肝纤维化程度的相关性。研究结果表明:随肝纤维化程度的不同,肝组织TGF-β1、血清TGF-β1表达水平、FBRS mRNA表达水平与肝脏胶原含量同步性升高(p<0.05)。进一步的相关分析表明:肝组织TGF-β1水平、FBRS mRNA与肝纤4项检查,即血清Ⅲ型前胶原(PC-Ⅲ)、Ⅳ型胶原片段(Ⅳ-C)、层粘连蛋白(LN)和透明质酸(HA)水平之间均呈正相关。本研究结果初步得出结论,慢性病毒性肝炎肝组织TGF-β1、血清TGF-β1表达水平、外周血FBRS的表达水平与肝组织纤维化程度呈正相关。 相似文献
992.
金兵 《基因组学与应用生物学》2019,(7):3346-3351
为了研究C-反应蛋白(CRP)、纤维蛋白原(FIB)及白细胞计数(WBC)与慢性阻塞性肺疾病急性(COPD)的相关性及用于诊断慢性阻塞性肺疾病的临床意义,本研究将2015年8月至2017年2月在本院呼吸与危重症医学科住院治疗的60例慢性阻塞性肺疾病急性加重期患者作为AECOPD组,并选择同期住院的60例慢性阻塞性肺疾病稳定期患者设为SCOPD组,60例健康人员作为健康对照组,用受试者工作特征曲线(receiver operator characteristic curve,ROC curve)分析血清CRP、FIB、WBC水平及诊断COPD疾病的临床价值。研究结果表明,AECOPD组及SCOPD组血清CRP、FIB及WBC水平均明显高于健康对照组(tCRP=7.14,tFIB=2.72,tWBC=9.82),AECOPD组血清CRP、FIB及WBC水平(tCRP=37.29,tFIB=5.28,tWBC=14.36)也明显高于SCOPD组(tCRP=14.45,tFIB=4.71,tWBC=12.77),差异均有统计学意义(均p<0.05)。同时,在SCOPD者中,CRP水平与FIB和WBC呈正相关(γ=0.687,0.512,均p<0.05),FIB和WBC也呈正相关(γ=0.445,0.512,p<0.05);在AECOPD组中,CRP水平与FIB和WBC呈正相关(γ=0.733,0.587,均p<0.05),FIB和WBC也具有相关性(γ=0.676,p<0.05)。本研究初步结论认为,CRP、FIB、WBC水平与COPD患者的病情严重程度存在明显相关性,联合CRP、FIB、WBC因子检测有助于鉴别COPD恶化程度,并可作为COPD疾病的监测指标。 相似文献
993.
《Cytokine》2015,72(2):207-214
Neuropathic pain is a debilitating condition caused by damage to the somatosensory nervous system, such as peripheral nerve injury. The immune system, and in particular the adaptive T cell response, plays a key role in mediating such pain. Regulatory T (Treg) cells are a small subpopulation of inhibitory T cells that prevent autoimmunity, limit immunopathology and maintain immune homeostasis. Here, we investigated the effects of conditional depletion of Treg cells on mechanical allodynia and serum cytokines in mice with chronic constriction injury (CCI) of the sciatic nerve, an animal model of neuropathic pain. We demonstrate that CCI induced the infiltration of small numbers of Treg cells within effected neuronal tissue. Utilising the transgenic DEREG (DEpletion of REGulatory T cells) mice, we confirmed effective depletion of Foxp3+ Treg cells by diphtheria toxin injections. Following CCI we observed a transient, though significant, increase in pain hypersensitivity for Treg-depleted DEREG mice compared to non-Treg-depleted mice. Analysis of systemic cytokine levels demonstrated significant changes in serum cytokine expression profiles. In particular, we observed significant increases in systemic concentration of RANTES, IL-2 and IL-5, and significant decreases in IL-12 and IFN-γ in nerve-injured Treg-depleted DEREG mice. Further analysis indicated a substantial increase in the serum concentration of IL-12p40 as a direct result of Treg cell depletion. These results suggest that depletion of Foxp3+ Treg cells promote nerve injury-induced pain hypersensitivity, partially by inducing altered systemic concentrations of cytokines, which may act to regulate neuropathic pain. 相似文献
994.
Emilienne Verkaeren Agnès Brion Amélie Hurbault Cécile Chenivesse Capucine Morelot-Panzini Jésus Gonzalez-Bermejo Valérie Attali Thomas Similowski Christian Straus 《Respiratory research》2015,16(1)
Background
Congenital central hypoventilation syndrome (CCHS) is a rare genetic disease due to PHOX2B mutations. CCHS patients suffer from many autonomic disorders, dominated clinically by defective ventilatory automatisms. From birth, the life of CCHS patients depends on ventilatory support during sleep, involving a high burden of care. Whether or not this impairs the quality of life of these patients during adulthood remains unknown.Methods
We applied the medical outcome study short form-36 (SF-36) to 12 CCHS patients aged 15–33 (9 women) at the time of their passage from pediatric to adult care. Scores for the SF-36 dimensions were compared to the age- and gender-matched French reference population after transformation into standardized Z-scores. The SF-36 physical component summary score (PCS) and mental component summary score (MCS) were compared to American reference values.Results
Median Z-scores were significantly different from zero for PF (physical functioning, p = 0.020) and GH (general health perception, p = 0.0342) and for PCS (p = 0.020). The other physical dimensions (RP, role limitation due to physical function; BP, bodily pain) and the mental dimensions (VT, vitality; SF, social functioning; RE, role limitation due to emotional function; MH, mental health) and MCS were not altered.Conclusions
We conclude that, despite the physical constraints imposed by CCHS and its anxiogenic nature, this disease is associated with an impairment of health-related quality of life in young adults that remains moderate. Whatever the underlying explanations, these results convey hope to parents with a child diagnosed with CCHS and for patients themselves. 相似文献995.
Fatemeh Karimi Ali Rafati Ali Noorafshan Leila Hosseini 《Chronobiology international》2019,36(4):510-516
Chronic Sleep Restriction (CSR) is known as a risk factor for cardiovascular diseases. However, the structural changes of Sinoatrial (SA) node cells have received less attention. This study aimed to evaluate the effects of CSR on SA node in an animal model using stereological methods. Adult male Sprague-Dawley rats were randomly divided into CSR, grid-floor, and control groups. The CSR procedure was designed such a way that the animals had a full cycle of sleep (6 hours) per day, while they were unable to have a Rapid Eye Movement (REM) sleep during the remaining 18 hours. This was induced by a multiplatform box containing water. The grid-floor animals were placed in the same multiplatform box with a grid-floor covering to prevent falling in water. After 21 days, the right atria were dissected out. Then, the location of the SA node was determined and evaluated by stereological techniques. The total volume of the SA node, the total volume of the main node cells, the volume of the connective tissue, and mean volume of the node cells were respectively enlarged by 60%, 47%, 68%, and 51% in the CSR animals compared to the grid-floor rats (p < 0.05). However, no significant changes were detected in these parameters in the control and grid-floor animals. The population of the main node cells remained constant in all animal groups. In addition, the three-dimensional reconstruction of the SA node in the CSR group showed a hypertrophied appearance. In conclusion, CSR induced hypertrophic changes in the rats’ SA node structures without alteration in the number of main node cells. 相似文献
996.
Swagat H. Sharma Juan Lorenzo Pablo Monica Suarez Montesinos Anna Greka Corey R. Hopkins 《Bioorganic & medicinal chemistry letters》2019,29(2):155-159
The transient receptor potential cation channel 5 (TRPC5) has been previously shown to affect podocyte survival in the kidney. As such, inhibitors of TRPC5 are interesting candidates for the treatment of chronic kidney disease (CKD). Herein, we report the synthesis and biological characterization of a series of N-heterocyclic-1-benzyl-1H-benzo[d]imidazole-2-amines as selective TRPC5 inhibitors. Work reported here evaluates the benzimidazole scaffold and substituents resulting in the discovery of AC1903, a TRPC5 inhibitor that is active in multiple animal models of CKD. 相似文献
997.
One of common pathophysiological states associated with central nervous system is chronic cerebral hypoperfusion (CH) that
frequently occurs in conditions such as vascular dementia and Alzheimer’s disease. Long term blockage of angiotensin II type
1 (AT1) receptor provides protection from ischemia induced injury of brain as well as reduction of cerebrovascular inflammation.
Examining effect of the blockage on reduced glutathione (GSH), ascorbic acid (AA), and lipid peroxidation were of purpose
in the present study. Modeling CH, rats were subjected to permanent occlusion of common carotid arteries bilaterally. AT1 receptor antagonist, candesartan, was given daily for 14 days after surgery. CH caused a significant increase in lipid peroxidation
and decrease in GSH content of cerebral hippocampal tissue with no change in AA level. Candesartan (0.5 mg/kg, oral) not only
reduced lipid peroxidation but also restored GSH significantly besides elevating AA and improving histopathological alterations.
In conclusion, long term AT1 receptor blockage may be considered as novel therapeutic approach for protection from damage associated with CH. Underlying
mechanism(s) may in part be related to suppressing oxidative stress and preserving brain antioxidant capacity. 相似文献
998.
Resveratrol, a red wine polyphenol, attenuates ethanol-induced oxidative stress in rat liver 总被引:4,自引:0,他引:4
Kasdallah-Grissa A Mornagui B Aouani E Hammami M El May M Gharbi N Kamoun A El-Fazaâ S 《Life sciences》2007,80(11):1033-1039
The involvement of oxidative stress in the pathogenesis of alcoholic diseases in the liver has been repeatedly confirmed. Resveratrol, a natural phytoalexin present in grape skin and red wine possesses a variety of biological activities including antioxidant. This study was conducted to evaluate whether resveratrol has a preventive effect on the main indicators of hepatic oxidative status as an expression of the cellular damage caused by free radicals, and on antioxidant defence mechanism during chronic ethanol treatment. Wistar rats were treated daily with 35% ethanol solution (3 g/kg/day i.p.) during 6 weeks and fed basal diet or basal diet containing 5 g/kg resveratrol. Control rats were treated with i.p. saline and fed basal diet. Experimentally, chronic ethanol administration leads to hepatotoxicity as monitored by the increase in the level of hepatic marker enzymes and the appearance of fatty change, necrosis, fibrosis and inflammation in liver sections. Ethanol also enhanced the formation of MDA in the liver indicating an increase in lipid peroxidation, a major end-point of oxidative damage, and caused drastic alterations in antioxidant defence systems. Particularly the activities of hepatic superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were found reduced by ethanol treatment while glutathione reductase (GR) activity was unchanged. Dietary supplementation with resveratrol during ethanol treatment inhibited hepatic lipid peroxidation and ameliorated SOD, GPx and CAT activities in the liver. Conclusively, we can suggest that resveratrol could have a beneficial effect in inhibiting the oxidative damage induced by chronic ethanol administration, which was proved by the experiments that we conducted on rats. 相似文献
999.
《European journal of cell biology》2022,101(4):151271
In the United States, the Centers for Disease Control and Prevention (CDC) terms HIV and tobacco use among the ten most important public health challenges we face today. In the last decade, there has been a remarkable decrease in the number of deaths due to HIV/AIDS, especially after the widespread availability and use of combination antiretroviral therapy (cART). However, people living with HIV/AIDS have a heightened risk of chronic complications and comorbidities, including neurological disorders. Around 40–60 % of HIV-infected individuals progress to NeuroAIDS, a group of disorders caused primarily by HIV-mediated damage to the central and peripheral nervous systems, despite receiving cART. The detrimental effects of chronic smoking on the cerebrovascular system are also well studied and reported. Addictive behavior, such as smoking, is more common in HIV patients compared to the general population. In this context, given the existing immune suppression, smoking can pose a significant risk for the progression of the disease to NeuroAIDS by disrupting the integrity of the blood-brain barrier (BBB). Here we show that co-treatment with Tobacco Smoke Extract (TSE) and HIV-1 gp120 (HIV envelope glycoprotein) in primary cultures of human brain microvascular endothelial cells promoted heightened cellular stress responses compared to control and individual treatments. Our findings suggest that a potential synergistic effect between smoke exposure and gp120 can worsen the loss of BBB viability, possibly exacerbating NeuroAIDS progression. 相似文献
1000.
摘要:慢性阻塞性肺疾病(COPD)是一种慢性炎症性呼吸道疾病,其特征是持续气流受限和肺部炎症反应异常。气道内微生物是COPD恶化的主要原因,并且使气道中的炎症反应持续存在而促成COPD进展,这导致肺功能的进一步损害和巨大的医疗保健成本。近年来随着高通量测序技术的发展和运用,人类肺微生物组的研究逐渐成为热点。大量研究表明,COPD患者肺内存在明显不同的微生物群落,而且与COPD的疾病严重程度及恶化状态有关。肺微生物组学的研究有助于人们更全面地理解COPD患者肺内的微生态系统及其在该病恶化和进展中的作用。本文就肺微生物组在COPD中的研究进展作一综述,并探讨未来的研究前景。 相似文献