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排序方式: 共有950条查询结果,搜索用时 15 毫秒
71.
Rubén Fernández-Santiago Manu SharmaDaniela Berg Thomas IlligJohanna Anneser Thomas MeyerAlbert Ludolph Thomas Gasser 《Neurobiology of aging》2011,32(3):551
A recent genome-wide association study (GWAS) found significant association of six single nucleotide polymorphisms (SNPs) in the gene FLJ10986 with sporadic amyotrophic lateral sclerosis (SALS). Another independent GWAS reported significant association of one SNP in the gene inositol 1,4,5-triphosphate receptor 2 (ITPR2) with SALS. These studies provided conflicting results. We examined the six most significant SNPs in FLJ10986 and one SNP in ITPR2 in a large cohort consisting of 595 SALS cases and 681 controls ascertained from Germany. Our results did not provide evidence for the association of these SNPs with SALS, suggesting a possible population-specific effect for FLJ10986 and ITPR2 that do not modulate the risk for SALS in the German population. 相似文献
72.
Research on biomarkers and genetics shares a number of objectives, including the identification of novel disease mechanisms, optimization of therapeutic studies, and improvement of diagnosis and prognosis. The latter is of particular relevance in neurodegenerative diseases where the underlying molecular processes often go on for decades until the first clinical symptoms appear. In this commentary we review the potential contribution that insight gained from genetic research may have on biomarker development in neurodegeneration. We argue that future progress will largely depend on a widespread application of novel high-throughput technologies now becoming available in both fields. 相似文献
73.
The sections in the following review cover six main neurodegenerative diseases. The first article on Alzheimer's disease (AD) outlines the major evidence available to date that links Aβ-amyloid peptide as a proximal cause of AD. The article also highlights how an initial finding of the protein content of the amyloid plaque seen in the brains of patients with AD has led to many very significant findings in the neuroscience field. The next section outlines the many and recent advances that have occurred in the field of frontotemporal lobar degeneration (FTLD), including the most recent finding related to the fused sarcoma gene (FUS) and the newest nomenclature whereby the FTLD is subtyped according to the presence of specific proteins seen at a microscopic level. The section on Lewy bodies outlines the latest advances in the relationship between the anatomical distribution of Lewy bodies and disease phenotype. The following section includes an overview of current known genetic links with familial causes of motor neuron disease (MND) and an update on the areas being researched into the causes of sporadic MND. The presence of TDP-43 within inclusions and its new diagnostic role in MND are discussed. The final article on prion diseases gives an overview of human prion diseases, including the phenotypic spectrum, epidemiology and diagnostic investigations relevant to disease. 相似文献
74.
Amyotrophic lateral sclerosis (ALS) is a progressive degenerative neuromuscular disease that presents with upper and lower motor neuron signs. Although the majority of ALS cases are sporadic, 10% are familial, of which 20%–25% result from mutations in the superoxide dismutase (SOD1) gene. We describe a novel case of SOD1 (A4V)‐mediated ALS that presented with lower motor neuron facial diplegia and unilateral vocal cord paralysis. This case expands the phenotypic expression of the A4V mutation. Muscle Nerve, 2009 相似文献
75.
Felix Geser Maria Martinez-Lage Linda K. Kwong Virginia M.-Y. Lee John Q. Trojanowski 《Journal of neurology》2009,256(8):1205-1214
Ever since the significance of pathological 43-kDa transactivating responsive sequence DNA-binding protein (TDP-43) for human
disease has been recognized in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin positive
inclusions (FTLD-U), a number of publications have emerged reporting on this pathology in a variety of neurodegenerative diseases.
Given the heterogeneous and, in part, conflicting nature of the recent findings, we here review pathological TDP-43 and its
relationship to human disease with a special focus on ALS and FTLD-U. To this end, we propose a classification scheme in which
pathological TDP-43 is the major disease defining pathology in one group, or is present in addition to other neurodegenerative
hallmark pathologies in a second category. We conclude that the TDP-43 proteinopathies represent a novel class of neurodegenerative
disorders akin to α-synucleinopathies and tauopathies, with the concept of ALS and FTLD-U to be widened to a broad clinico-pathological
multisystem disease, i.e., TDP-43 proteinopathy. 相似文献
76.
P. Wicks S. Abrahams B. Papps A. Al-Chalabi C. E. Shaw P. N. Leigh L. H. Goldstein 《Journal of neurology》2009,256(2):234-241
Background
Sporadic Amyotrophic Lateral Sclerosis (sALS) is associated with frontotemporal dementia (ALS-FTD) or milder deficits of cognitive
(predominantly executive) dysfunction (ALSCi) in some patients. Some forms of familial ALS (FALS) have a family history of
FTD, ALS-FTD, or both, but there have been few reports of ALS-FTD in FALS patients with mutations of the gene superoxide dismutase-1
(SOD1 FALS). The aim of this study was to test the hypothesis that ALSCi may be found in non-SOD1 FALS, but that SOD1 FALS
patients would show little or no evidence of cognitive change.
Methods
A neuropsychological test battery was administered to 41 SALS patients, 35 control participants, 7 FALS patients with a SOD1
mutation (SOD1 FALS) and 10 FALS patients without a SOD1 mutation (non-SOD1 FALS).
Results
Relative to control participants, non-SOD1 FALS patients had impaired performance on written verbal fluency and confrontation
naming, and reported higher levels of executive behavioural problems. These deficits were absent in SOD1 FALS patients. SALS
patients performed poorer than controls only on the Graded Naming Test. All ALS groups had higher levels of behavioural apathy
and emotional lability than were found in control participants. Cognitive domains of memory, receptive language, and visuospatial
perception were spared. Groups were matched for age, gender, premorbid full-scale IQ, anxiety and depression.
Discussion
Individuals with SOD1 gene mutations are less likely to have significant cognitive changes compared to non-SOD1 FALS patients.
Cognitive abnormalities in ALS are heterogeneous and may reflect underlying genetic variations rather than a simple spectrum
of extra-motor involvement. 相似文献
77.
目的:探讨肌萎缩侧索硬化症(ALS)与脊髓型颈椎病(CSM)的神经电生理鉴别诊断方法。方法:回顾性分析经临床确诊的23例ALS及28例CSM患者的神经电生理表现。结果:在神经电图检查中,ALS组除12例运动神经动作电位降低外,其余各项指标正常;CSM组病例中,既有运动及感觉神经传导速度减慢,也有动作电位降低及末梢潜伏期延长。肌电图(EMG)检查结果显示:ALS组异常率高于CSM组(P〈0.05),且ALS组胸锁乳突肌及胫前肌异常率均显著高于CSM组(P〈0.01),但胫前肌异常的4例CSM均合并有腰椎间盘突出。结论:对于临床拟诊为CSM患者有必要常规加作胸锁乳突肌EMG,这不仅有助于CSM与ALS的鉴别诊断,对于指导两者的治疗及预后判断也具有十分重要的意义。 相似文献
78.
目的:探讨肌萎缩侧索硬化症(ALS)患者的临床特点、肌电图(EMG)和神经传导速度(NCV)对ALS的诊断价值。方法:对42例ALS患者回顾性分析其临床特点、NCV及其胸锁乳突肌、胸段脊旁肌及肢体肌EMG资料。结果:42例患者均呈广泛神经原性损害,胸锁乳突肌EMG异常率为90%,胸椎旁肌EMG异常率为88%,两者异常率均低于上、下肢肌EMG的异常率(100%,98%),而胸椎旁肌自发电位异常率又高于胸锁乳突肌。结论:早期EMG及NCV检查有助于ALS的早期确诊,行胸锁乳突肌及胸椎脊旁肌EMG检测对ALS的诊断及鉴别诊断有重要价值。 相似文献
79.
Sorarù G Vergani L Fedrizzi L D'Ascenzo C Polo A Bernazzi B Angelini C 《Neuropathology and applied neurobiology》2007,33(2):204-211
The pathogenesis of amyotrophic lateral sclerosis (ALS) is poorly understood. Increased levels of free radicals derived from nitric oxide (NO), the product of nitric oxide synthase (NOS), may damage mitochondrial function leading to motor neurone death. Previous studies demonstrated a specific impairment of mitochondrial function in skeletal muscle of ALS patients. In order to verify a pathogenetic relationship between neuronal NOS (nNOS) and mitochondrial function, we studied nNOS expression by Western blot and mitochondrial enzyme activity by spectrophotometric assays in muscle biopsies of 16 sporadic ALS patients and 16 controls subjects. We observed a reduced activity of respiratory chain complexes with mitochondrial encoded subunits and a lower nNOS amount in ALS muscles. There was a direct correlation between levels of nNOS and values of mitochondrial enzymes function. In ALS muscles we found normal levels of manganese superoxide dismutase (SOD2) that is assumed as related to mitochondrial DNA abnormalities. Our data suggest a beneficial role for NO to mitochondrial function and lead to the hypothesis of a common oxidative damage in motor neurones and skeletal muscle in sporadic ALS patients. 相似文献
80.
Van Vught PW Van Wijk J Bradley TE Plasmans D Jakobs ME Veldink JH de Jong JM Van den Berg LH Baas F 《Neuromuscular disorders : NMD》2007,17(11-12):964-967
Growth factors, such as ciliary neurotrophic factor (CNTF), have been implicated in neuronal survival and proliferation. About 2% of the human population is homozygous for a polymorphism that induces truncated and biologically inactive CNTF but does not obviously change the phenotype. In a population of patients with hereditary neuropathy, a higher rate of the CNTF null mutation would indicate greater susceptibility for clinically significant disease, and a recent report attributes early onset and rapid deterioration in a case of familial ALS (FALS) to this mutation. We have, therefore, genotyped the CNTF polymorphism in a large group of patients with CMT 1a, HNPP, sporadic ALS, in one pedigree with FALS, and controls. All groups exhibited a similar distribution of the polymorphism. We conclude that absence of CNTF does not increase susceptibility for these disorders and confirm that it does not affect onset and course of familial and sporadic ALS. 相似文献