全文获取类型
收费全文 | 394篇 |
免费 | 48篇 |
国内免费 | 5篇 |
出版年
2024年 | 3篇 |
2023年 | 18篇 |
2022年 | 8篇 |
2021年 | 28篇 |
2020年 | 25篇 |
2019年 | 26篇 |
2018年 | 23篇 |
2017年 | 24篇 |
2016年 | 16篇 |
2015年 | 13篇 |
2014年 | 14篇 |
2013年 | 28篇 |
2012年 | 28篇 |
2011年 | 15篇 |
2010年 | 11篇 |
2009年 | 18篇 |
2008年 | 19篇 |
2007年 | 15篇 |
2006年 | 15篇 |
2005年 | 16篇 |
2004年 | 9篇 |
2003年 | 7篇 |
2002年 | 10篇 |
2001年 | 9篇 |
2000年 | 8篇 |
1999年 | 7篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
排序方式: 共有447条查询结果,搜索用时 15 毫秒
11.
12.
13.
14.
15.
Talia Fuchs Julian N. Trollor John Crawford David A. Brown Bernhard T. Baune Katherine Samaras Lesley Campbell Samuel N. Breit Henry Brodaty Perminder Sachdev Evelyn Smith 《Aging cell》2013,12(5):882-889
Higher levels of macrophage inhibitory cytokine‐1, also known as growth differentiation factor 15 (MIC‐1/GDF15), are associated with adverse health outcomes and all‐cause mortality. The aim of this study was to examine the relationships between MIC‐1/GDF15 serum levels and global cognition, five cognitive domains, and mild cognitive impairment (MCI), at baseline (Wave 1) and prospectively at 2 years (Wave 2), in nondemented participants aged 70–90 years. Analyses were controlled for age, sex, education, Framingham risk score, history of cerebrovascular accident, acute myocardial infarction, angina, cancer, depression, C‐reactive protein, tumor necrosis factor‐α, interleukins 6 and 12, and apolipoprotein ε4 genotype. Higher MIC‐1/GDF15 levels were significantly associated with lower global cognition at both waves. Cross‐sectional associations were found between MIC‐1/GDF15 and all cognitive domains in Wave 1 (all P < 0.001) and between processing speed, memory, and executive function in Wave 2 (all P < 0.001). Only a trend was found for the prospective analyses, individuals with high MIC‐1/GDF15 at baseline declined in global cognition, executive function, memory, and processing speed. However, when categorizing MIC‐1/GDF15 by tertiles, prospective analyses revealed statistically significant lower memory and executive function in Wave 2 in those in the upper tertile compared with the lower tertile. Receiver operating characteristics (ROC) analysis was used to determine MIC‐1/GDF15 cutoff values associated with cognitive decline and showed that a MIC‐1/GDF15 level exceeding 2764 pg/ml was associated with a 20% chance of decline from normal to MCI or dementia. In summary, MIC‐1/GDF15 levels are associated with cognitive performance and cognitive decline. Further research is required to determine the pathophysiology of this relationship. 相似文献
16.
17.
MicroRNA-132 (miR-132) has been shown to participate in many diseases. This study aimed to understand the correlation between the level of miR-132 and the severity of dementia post-ischemic stroke. An online tool ( www.mirdb.org ) was used to find the miR-132 binding site in acetylcholinesterase (ACHE) 3′-untranslated region (UTR), followed by a luciferase reporter assay to validate ACHE as a miR-132 target. A similar relationship between miR-132 and ACHE was also established in cerebrospinal fluid samples collected from human subjects. A negative correlation was established between ACHE and miR-132 by measuring the relative luciferase activity. Meanwhile, Western blot analysis and real-time polymerase chain reaction were also conducted to compare the levels of ACHE messenger RNA and protein between two groups (dementia positive, n = 26 and dementia negative, n = 26) or among cells treated with miR-132 mimics, ACHE small interfering RNA, and miR-132 inhibitors. As shown in the results, miR-132 can reduce the expression of ACHE. Further experiments were also carried out to study the effect of miR-132 and ACHE on cell viability and apoptosis, and the results demonstrated that miR-132 enhanced cell viability while suppressing apoptosis. In addition, ACHE reduced cell viability while promoting apoptosis. miR-132 targeted ACHE and suppressed its expression. Additionally, miR-132 and ACHE have been shown to affect the cell viability and apoptosis in the central nervous system. 相似文献
18.
Objectives
Progressive dementia is a rare phenotypic feature of female X-ALD carriers. Even rarer is the additional presence of further risk factors for dementia, such as diabetes, hypothyroidism, and hepatopathy. We report a unique female X-ALD carrier presenting with severe, progressive dementia, paraspasticity, sphincteric dysfunction, and multisystem disease.Case report
A 79 years-old female with a history of strumectomy, diabetes, hepatopathy, hypothyroidism, arterial hypertension, hiatal hernia, left retinal ablation, ovariectomy, hysterectomy, osteoporosis, bilateral hip endoprosthesis, and neurogenic bladder dysfunction developed slowly progressive cognitive decline since age of 77 years. She had been identified as a female carrier of X-ALD in 12/2010 upon a family screening. At age of 79 years she presented with severe dementia, anxiety, unsteadiness, helplessness, hypertelorism, exaggerated patella tendon reflexes, reduced Achilles tendon reflexes, club feet, contractures of the ankles, the knees, and the hips, and the inability to stay or walk. Cerebral CT showed diffuse atrophy, demyelination periventricularly, small lacunas in the basal ganglia, and small calcifications of the basal ganglia and the temporal lobe on the right side. Differential diagnoses of dementia were considered but were all excluded upon the clinical presentation, blood chemical investigations, imaging studies, and the pattern of neuropsychological deficits.Conclusions
With progression of the disease manifesting X-ALD carriers may develop progressive severe dementia, severe paraspasticity, and sphincteric dysfunction. Female carriership of X-ALD can be a differential diagnosis of dementia. 相似文献19.
Alexandra M. Nicholson NiCole A. Finch Aleksandra Wojtas Matt C. Baker Ralph B. Perkerson III Monica Castanedes‐Casey Linda Rousseau Luisa Benussi Giuliano Binetti Roberta Ghidoni Ging‐Yuek R. Hsiung Ian R. Mackenzie Elizabeth Finger Bradley F. Boeve Nilüfer Ertekin‐Taner Neill R. Graff‐Radford Dennis W. Dickson Rosa Rademakers 《Journal of neurochemistry》2013,126(6):781-791
Frontotemporal lobar degeneration (FTLD) is the second leading cause of dementia in individuals under age 65. In many patients, the predominant pathology includes neuronal cytoplasmic or intranuclear inclusions of ubiquitinated TAR DNA binding protein 43 (FTLD‐TDP). Recently, a genome‐wide association study identified the first FTLD‐TDP genetic risk factor, in which variants in and around the TMEM106B gene (top SNP rs1990622) were significantly associated with FTLD‐TDP risk. Intriguingly, the most significant association was in FTLD‐TDP patients carrying progranulin (GRN) mutations. Here, we investigated to what extent the coding variant, rs3173615 (p.T185S) in linkage disequilibrium with rs1990622, affects progranulin protein (PGRN) biology and transmembrane protein 106 B (TMEM106B) regulation. First, we confirmed the association of TMEM106B variants with FTLD‐TDP in a new cohort of GRN mutation carriers. We next generated and characterized a TMEM106B‐specific antibody for investigation of this protein. Enzyme‐linked immunoassay analysis of progranulin protein levels showed similar effects upon T185 and S185 TMEM106B over‐expression. However, over‐expression of T185 consistently led to higher TMEM106B protein levels than S185. Cycloheximide treatment experiments revealed that S185 degrades faster than T185 TMEM106B, potentially due to differences in N‐glycosylation at residue N183. Together, our results provide a potential mechanism by which TMEM106B variants lead to differences in FTLD‐TDP risk.
20.
Neurocardiovascular instability (NCVI) refers to abnormal neural control of the cardiovascular system affecting blood pressure and heart rate behavior. Autonomic dysfunction and impaired cerebral autoregulation in aging contribute to this phenomenon characterized by hypotension and bradyarrhythmia. Ultimately, this increases the risk of falls and syncope in older people. NCVI is common in patients with neurodegenerative disorders including dementia. This review discusses the various syndromes that characterize NCVI icluding hypotension, carotid sinus hypersensitivity, postprandial hypotension and vasovagal syncope and how they may contribute to the aetiology of cognitive decline. Conversely, they may also be a consequence of a common neurodegenerative process. Regardless, recognition of their association is paramount in optimizing management of these patients. 相似文献