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排序方式: 共有111条查询结果,搜索用时 78 毫秒
41.
Krüger R Vieira-Säcker AM Kuhn W Müller T Woitalla D Schöls L Przuntek H Epplen JT Riess O 《Journal of neural transmission (Vienna, Austria : 1996)》1999,106(2):159-163
Summary. Recently a mutation in the parkin gene has been identified as the cause for an autosomal-recessively inherited form of early
onset Parkinson's disease (EOPD). The disease causing minimal deletion has been defined as a homozygous exon 4 loss in the
parkin gene among Japanese patients. We investigated 140 sporadic and familial EOPD patients of German ancestry for the exon
4 deletion in the parkin gene. None of our patients exhibited a homo-zygous deletion of exon 4, suggesting a minor role of
this mutation for EOPD in Caucasians. Nevertheless a detailed mutation analysis is warranted to explore the overall significance
of mutations in the parkin gene in EOPD.
Received September 18, 1998; accepted November 26, 1998 相似文献
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43.
Marco Onofrj MD Angelo Di Iorio MD PhD Claudia Carrarini MD Mirella Russo MD Raffaella Franciotti PhD Alberto J. Espay MD MSc Laura S. Boylan MD John-Paul Taylor MD PhD Massimo Di Giannantonio MD Giovanni Martinotti MD PhD Enza M. Valente MD PhD Astrid Thomas MD PhD Laura Bonanni MD PhD Stefano Delli Pizzi PhD Fedele Dono MD StefanoL. Sensi MD PhD 《Movement disorders》2021,36(12):2840-2852
44.
Takamatsu Y Shiotsuki H Kasai S Sato S Iwamura T Hattori N Ikeda K 《Current Neuropharmacology》2011,9(1):96-99
MDMA (3,4-methylenedioxymethamphetamine) is reportedly severely toxic to both dopamine (DA) and serotonin neurons. MDMA significantly reduces the number of DA neurons in the substantia nigra, but not in the nucleus accumbens, indicating that MDMA causes selective destruction of DA neurons in the nigrostriatal pathway, sparing the mesolimbic pathway. Parkinson's disease (PD) is a neurodegenerative disorder of multifactorial origin. The pathological hallmark of PD is the degeneration of DA neurons in the nigrostriatal pathway. Mutations in the parkin gene are frequently observed in autosomal recessive parkinsonism in humans. Parkin is hypothesized to protect against neurotoxic insult, and we attempted to clarify the role of parkin in MDMA-induced hyperthermia, one of the causal factors of neuronal damage, using parkin knockout mice. Body temperature was measured rectally before and 15, 30, 45, and 60 min after intraperitoneal injection of MDMA (30 mg/kg) at an ambient temperature of 22 ± 2°C. Significantly enhanced hyper-thermia after MDMA injection was observed in heterozygous and homozygous parkin knockout mice compared with wildtype mice, suggesting that parkin plays a protective role in MDMA neurotoxicity. 相似文献
45.
Non-motor behavioural impairments in parkin-deficient mice 总被引:1,自引:0,他引:1
Zhu XR Maskri L Herold C Bader V Stichel CC Güntürkün O Lübbert H 《The European journal of neuroscience》2007,26(7):1902-1911
Mutations in the parkin gene are the major cause of early-onset familial Parkinson's disease (PD). We previously reported the generation and analysis of a knockout mouse carrying a deletion of exon 3 in the parkin gene. F1 hybrid pa+/- mice were backcrossed to wild-type C57Bl/6 for three more generations to establish a pa-/-(F4) mouse line. The appearance of tyrosine hydroxylase-positive neurons was normal in young and aged pa-/- (F4) animals. Loss of parkin function in mice did not enhance vulnerability of dopaminergic neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity. However, the pa-/- (F4) mice displayed impaired exploration and habituation to a new environment and exhibited thigmotaxis behaviour in the open field and Morris water maze. Abnormal anxiety-related behaviour of pa-/- (F4) mice was also observed in the light/dark exploration test paradigm. Dopamine metabolism was enhanced in the striatum of pa-/- (F4) mice, as revealed by increased homovanillic acid (HVA) content and a reduced ratio of dihydroxyphenylacetic acid (DOPAC)/HVA. The alterations found in the dopaminergic system could be responsible for the behavioural impairments of pa-/- (F4) mice. Consistent with a recent observation of cognitive dysfunction in parkin-linked patients with PD, our findings provide evidence of a physiological role of parkin in non-motor behaviour, possibly representing a disease stage that precedes dopaminergic neuron loss. 相似文献
46.
《Expert opinion on therapeutic targets》2013,17(10):1133-1144
Introduction: Parkinson's disease (PD) is one of the most common neurodegenerative diseases affecting an increasing number of people worldwide with the ageing society. Although the etiology of PD remains largely unknown, it is now clear that genetic factors contribute to the pathogenesis of the disease. Recently, several causative genes have been identified in mendelian forms of PD. Growing evidence indicates that their gene products play important roles in oxidative stress response, mitochondrial function, and the ubiquitin–proteasome system, which are also implicated in idiopathic PD, suggesting that these gene products share a common pathway to nigral degeneration in both familial and idiopathic PD. However, treatment options are currently limited. Areas covered: Recently, a possible role of parkin, a gene product of PARK2-liked PD, in neuroprotection has been suggested. To this regard, several investigations have focused on the possible contribution of parkin in neurotoxic insults. In this article, the role of parkin in the pathogenesis of PD and the potential of parkin as a therapeutic target in PD will be discussed. Expert opinion: There is an urgent need to develop novel therapeutic options to better manage patients with PD. The data discussed in this article provide rationale for parkin as a therapeutic target. 相似文献
47.
Uwe Walter Christine Klein Ruediger Hilker Reiner Benecke Peter P Pramstaller Dirk Dressler 《Movement disorders》2004,19(12):1445-1449
Substantia nigra (SN) hyperechogenicity on brain parenchyma sonography (BPS) is highly characteristic for idiopathic PD. We studied 7 symptomatic and 7 asymptomatic parkin mutation carriers (PMC) from a large kindred with adult-onset parkinsonism. BPS revealed larger SN echogenic sizes in PMC with parkin mutations on both alleles (homozygous, compound-heterozygous), compared to PMC with only one mutated allele (Mann-Whitney U test, P = 0.007). In symptomatic PMC, larger SN echogenic size was correlated with younger age at onset of the disease (Spearman rank correlation, Rho = -0.937, P = 0.002) but not with age, disease duration, or disease severity. BPS demonstrated SN hyperechogenicity, in concordance with abnormal nigrostriatal (18)F-dopa positron emission tomography (PET), in all symptomatic and 3 asymptomatic PMC. In 2 asymptomatic PMC, PET and BPS were normal. However, in another 2 asymptomatic PET-normal PMC, SN hyperechogenicity could be detected. Data suggest SN hyperechogenicity as an early marker to detect preclinical parkinsonism. 相似文献
48.
Marked variation in clinical presentation and age of onset in a family with a heterozygous parkin mutation. 总被引:2,自引:0,他引:2
Louis C Tan Caroline M Tanner Rong Chen Piu Chan Matthew Farrer John Hardy J William Langston 《Movement disorders》2003,18(7):758-763
Parkin gene mutations have been detected in families with early-onset autosomal recessive parkinsonism. We report a novel heterozygous 40 base pair deletion in exon 3 of the parkin gene that increases the susceptibility of carriers to develop parkinsonism/dystonia and manifests remarkable variability in regard to age of onset and phenotype in a single family. After identifying the new mutation in the proband of this kindred, family members were contacted and evaluated by a movement disorders specialist using standardized protocols and prospectively set diagnostic criteria. Importantly, examining physicians and family members were blinded to the genetic testing. Five affected members in two generations carried the parkin mutation. The proband and one of his brothers had disease onset at 24 years of age while another brother had disease at age 44. One exhibited multi-focal dystonia and parkinsonism of 17 years duration, another suffered a unilateral slowly progressive parkinsonism over 13 years while the third suffered dystonia-parkinsonism of recent onset. A sibling pair in the preceding generation had mild previously undiagnosed parkinsonism. Clinicians should be aware that patients carrying a parkin gene mutation may present with dystonia-parkinsonism or very subtle parkinsonism with a markedly varied age of onset. 相似文献
49.
50.
目的 探讨parkin在阿尔茨海默病(AD)发病机制中的作用.方法 利用经典的GAL4/UAS系统,选用ninaEGAL4启动子,将突变位点在R406W处的Tau蛋白在果蝇复眼内选择性表达,构建ninaE-GAL4/UAS系统AD转基因果蝇模型.然后分别在敲除和不敲除线粒体分裂蛋白Drp1情况下,使parkin在AD转基因果蝇模型中表达.结果 parkin明显抑制了AD转基因果蝇模型复眼视网膜光感受神经元变性,而在Drp1被敲除后,parkin的保护作用效果明显减弱.结论 parkin对AD转基因果蝇模型具有神经保护作用,而这种神经保护作用可能需要依赖线粒体分裂蛋白Drp1的功能. 相似文献