全文获取类型
收费全文 | 2088篇 |
免费 | 185篇 |
国内免费 | 218篇 |
专业分类
儿科学 | 23篇 |
妇产科学 | 30篇 |
基础医学 | 186篇 |
临床医学 | 81篇 |
内科学 | 139篇 |
皮肤病学 | 1篇 |
神经病学 | 1063篇 |
特种医学 | 11篇 |
外科学 | 53篇 |
综合类 | 142篇 |
现状与发展 | 1篇 |
预防医学 | 34篇 |
眼科学 | 167篇 |
药学 | 426篇 |
1篇 | |
中国医学 | 123篇 |
肿瘤学 | 10篇 |
出版年
2024年 | 6篇 |
2023年 | 29篇 |
2022年 | 40篇 |
2021年 | 92篇 |
2020年 | 82篇 |
2019年 | 65篇 |
2018年 | 72篇 |
2017年 | 91篇 |
2016年 | 80篇 |
2015年 | 101篇 |
2014年 | 131篇 |
2013年 | 251篇 |
2012年 | 129篇 |
2011年 | 164篇 |
2010年 | 164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 | 37篇 |
2000年 | 26篇 |
1999年 | 19篇 |
1998年 | 27篇 |
1997年 | 18篇 |
1996年 | 13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2491条查询结果,搜索用时 31 毫秒
61.
Receptor interacting protein kinase mediates necrotic cone but not rod cell death in a mouse model of inherited degeneration 总被引:1,自引:0,他引:1
Y Murakami H Matsumoto M Roh J Suzuki T Hisatomi Y Ikeda JW Miller DG Vavvas 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(36):14598-14603
Retinitis pigmentosa comprises a group of inherited retinal photoreceptor degenerations that lead to progressive loss of vision. Although in most cases rods, but not cones, harbor the deleterious gene mutations, cones do die in this disease, usually after the main phase of rod cell loss. Rod photoreceptor death is characterized by apoptotic features. In contrast, the mechanisms and features of subsequent nonautonomous cone cell death remain largely unknown. In this study, we show that receptor-interacting protein (RIP) kinase mediates necrotic cone cell death in rd10 mice, a mouse model of retinitis pigmentosa caused by a mutation in a rod-specific gene. The expression of RIP3, a key regulator of programmed necrosis, was elevated in rd10 mouse retinas in the phase of cone but not rod degeneration. Although rd10 mice lacking Rip3 developed comparable rod degeneration to control rd10 mice, they displayed a significant preservation of cone cells. Ultrastructural analysis of rd10 mouse retinas revealed that a substantial fraction of dying cones exhibited necrotic morphology, which was rescued by Rip3 deficiency. Additionally, pharmacologic treatment with a RIP kinase inhibitor attenuated histological and functional deficits of cones in rd10 mice. Thus, necrotic mechanisms involving RIP kinase are crucial in cone cell death in inherited retinal degeneration, suggesting the RIP kinase pathway as a potential target to protect cone-mediated central and peripheral vision loss in patients with retinitis pigementosa. 相似文献
62.
Jiang J Ganesh T Du Y Quan Y Serrano G Qui M Speigel I Rojas A Lelutiu N Dingledine R 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(8):3149-3154
With interest waning in the use of cyclooxygenase-2 (COX-2) inhibitors for inflammatory disease, prostaglandin receptors provide alternative targets for the treatment of COX-2-mediated pathological conditions in both the periphery and the central nervous system. Activation of prostaglandin E2 receptor (PGE(2)) subtype EP2 promotes inflammation and is just beginning to be explored as a therapeutic target. To better understand physiological and pathological functions of the prostaglandin EP2 receptor, we developed a suite of small molecules with a 3-aryl-acrylamide scaffold as selective EP2 antagonists. The 12 most potent compounds displayed competitive antagonism of the human EP2 receptor with K(B) 2-20 nM in Schild regression analysis and 268- to 4,730-fold selectivity over the prostaglandin EP4 receptor. A brain-permeant compound completely suppressed the up-regulation of COX-2 mRNA in rat cultured microglia by EP2 activation and significantly reduced neuronal injury in hippocampus when administered in mice beginning 1 h after termination of pilocarpine-induced status epilepticus. The salutary actions of this novel group of antagonists raise the possibility that selective block of EP2 signaling via small molecules can be an innovative therapeutic strategy for inflammation-related brain injury. 相似文献
63.
Koh PO 《Journal of pineal research》2012,52(1):57-61
Melatonin is an antioxidant that has neuroprotective functions in ischemic brain injury. Protein phosphatase 2A (PP2A) is a serine and threonine phosphatase that modulates cell metabolism and cell survival. This study investigated whether melatonin modulates PP2A subunit B in focal cerebral ischemia and glutamate toxicity-induced neuronal cell death in a rat model. Middle cerebral artery occlusion (MCAO) was performed to induce permanent cerebral ischemic injury. Adult male rats were treated with vehicle or melatonin (5 mg/kg) prior to MCAO, and cerebral cortex tissues were collected 24 hr after MCAO. A proteomic approach elucidated the decrease in PP2A subunit B in MCAO-operated animals. Melatonin treatment attenuated injury-induced reductions in PP2A subunit B levels. Western blot analyses indicated that melatonin prevents injury-induced decrease in PP2A subunit B levels. In neuronal cells, glutamate toxicity induced a lowering of PP2A subunit B, while melatonin treatment attenuated the glutamate exposure-induced decreases in PP2A subunit B. These results suggest that the maintenance of PP2A subunit B by melatonin in ischemic injury is critical to the neuroprotective function of melatonin during neuronal cell damage. 相似文献
64.
《The world journal of biological psychiatry》2013,14(5):340-348
AbstractObjectives. More than 60 years have passed since the introduction of lithium into modern psychiatry and special issues of Bipolar Disorders in 2009 and Neuropsychobiology in 2010 were devoted to this anniversary. Notwithstanding such a long tradition, a number of key articles on the neuropsychiatric aspects of lithium have appeared in recent years. Methods. This update was based on the most important original papers and reviews on lithium published in recent years. The main topics were the efficacy of lithium in mood disorders, with a special focus on cognitive functions, the neuroprotective effects of this ion and the potential of using lithium in neurology. Results. Clinical studies and reviews point to lithium being still a cornerstone for the prophylaxis of mood disorders, especially bipolar. The pro-cognitive and antisuicidal properties of lithium have been confirmed as an augmentation of antidepressants in treatment-resistant depression. The neuroprotective effects of lithium have been evidenced in both experimental research and in clinical studies using brain imaging. The possible use of lithium in the prophylaxis of dementia and in neurodegenerative disorders, such as Huntington's disease and amyotrophic lateral sclerosis is discussed. Conclusions. Although not promoted by pharmaceutical companies, lithium remains a highly important drug in neuropsychiatry. 相似文献
65.
66.
Abnormal TAR DNA-binding protein 43 (TDP-43) inclusion bodies can be detected in the degen- erative neurons of amyotrophic lateral sclerosis. In this study, we induced chronic oxidative stress injury by applying malonate to cultured mouse cortical motor neurons. In the later stages of the malonate insult, TDP-43 expression reduced in the nuclei and transferred to the cytoplasm. This was accompanied by neuronal death, mimicking the pathological changes in TDP-43 that are seen in patients with amyotrophic lateral sclerosis. Interestingly, in the early stages of the response to malonate treatment, nuclear TDP-43 expression increased, and neurons remained relatively intact, without inclusion bodies or fragmentation. Therefore, we hypothesized that the increase of nuclear TDP-43 expression might be a pro-survival factor against oxidative stress injury. This hypothesis was confirmed by an in vitro transgenic experiment, in which overexpression of wild type mouse TDP-43 in cultured cortical motor neurons significantly reduced malonate-induced neuronal death. Our findings suggest that the loss of function of TDP-43 is an important cause of neuronal degen- eration, and upregulation of nuclear TDP-43 expression might be neuroprotective in amyotrophic lateral sclerosis. 相似文献
67.
68.
69.
70.
Ya-Lei Ning Nan Yang Xing Chen Ren-Ping Xiong Xiu-Zhu Zhang Ping Li Yan Zhao Xing-Yun Chen Ping Liu Yan Peng Zheng-Guo Wang Jiang-Fan Chen Yuan-Guo Zhou 《Journal of cerebral blood flow and metabolism》2013,33(11):1789-1798
Traumatic brain injury (TBI), particularly explosive blast-induced TBI (bTBI), has become the most prevalent injury among military personnel. The disruption of cognitive function is one of the most serious consequences of bTBI because its long-lasting effects prevent survivors fulfilling their active duty and resuming normal civilian life. However, the mechanisms are poorly understood and there is no treatment available. This study investigated the effects of adenosine A2A receptor (A2AR) on bTBI-induced cognitive deficit, and explored the underlying mechanisms. After being subjected to moderate whole-body blast injury, mice lacking the A2AR (A2AR knockout (KO)) showed less severity and shorter duration of impaired spatial reference memory and working memory than wild-type mice did. In addition, bTBI-induced cortical and hippocampal lesions, as well as proinflammatory cytokine expression, glutamate release, edema, cell loss, and gliosis in both early and prolonged phases of the injury, were significantly attenuated in A2AR KO mice. The results suggest that early injury and chronic neuropathological damages are important mechanisms of bTBI-induced cognitive impairment, and that the impairment can be attenuated by preventing A2AR activation. These findings suggest that A2AR antagonism is a potential therapeutic strategy for mild-to-moderate bTBI and consequent cognitive impairment. 相似文献