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排序方式: 共有113条查询结果,搜索用时 15 毫秒
1.
A case of acute lymphoblastic leukaemia, associated with cells resembling Gaucher cells in the bone marrow, is reported. The patient had no evidence of inherited Gaucher's disease and the ultrastructural appearance of the cells was consistent with pseudo-Gaucher cells described in other haematological diseases. This is the first report of these cells in association with acute lymphoblastic leukaemia. 相似文献
2.
Tian J Shi J Bailey K Harris JM Pritchard A Lambert JC Chartier-Harlin MC Pickering-Brown SM Lendon CL Mann DM 《Neuroscience letters》2004,354(2):103-106
The impact of the insertion (I)/deletion (D) (I/D) polymorphism in the angiotensin 1-converting enzyme (ACE) gene on the extent of white matter myelin loss (ML) was investigated in four regions of the cerebral cortex in an autopsy-confirmed series of 93 patients with Alzheimer's disease (AD). The possible influence of APO E epsilon4 allele acting in concert with ACE D allele was assessed. The extent of ML did not differ between D/D, I/D and I/I genotype groups when data from all four brain regions were combined. However, separate analysis showed that the frontal and temporal cortex tended to be affected more severely by ML in patients with D/D genotype compared to those with I/D and I/I genotypes. Stratification according to APO E epsilon4 allele revealed a greater overall ML in patients bearing at least one copy of ACE D allele and one APO E epsilon4 allele, especially in individuals homozygous for both. The APO E epsilon4 allele may therefore act synergistically in patients with AD (and other subjects) bearing ACE D/D genotype to increase the risk of ML, perhaps through transient ischaemic episodes consequent upon poor cardiac output associated with coronary atherosclerosis in patients with the APO E epsilon4 allele. 相似文献
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Lambert D Middle F Hamshere ML Segurado R Raybould R Corvin A Green E O'Mahony E Nikolov I Mulcahy T Haque S Bort S Bennett P Norton N Owen MJ Kirov G Lendon C Jones L Jones I Holmans P Gill M Craddock N 《Molecular psychiatry》2005,10(9):831-841
Bipolar affective disorder (BPAD) is a common psychiatric disorder with complex genetic aetiology. We have undertaken a genome-wide scan in one of the largest samples of bipolar affected sibling pairs (ASPs) using a two-stage approach combining sample splitting and marker grid tightening. In this second stage analysis, we have examined 17 regions that achieved a nominally significant maximum likelihood LOD score (MLS) threshold of 0.74 (or 1.18 for the X-chromosome) in stage one. The second stage has added 135 ASP families to bring the total stage 2 sample to 395 ASPs. In total, 494 microsatellite markers have been used to screen the human genome at a density of 10 cM in the first stage sample (260 ASPs) and 5 cM in the second stage. Under the broad diagnostic model, two markers gave LOD scores exceeding 3 with two-point analysis: D4S392 (LOD=3.30) and D10S197 (LOD=3.18). Multipoint analysis demonstrated suggestive evidence of linkage between BPAD and chromosomal regions 6q16-q21 (MLS=2.61) and 4q12-q21 (MLS=2.38). 6q16-q21 is of particular interest because our data, together with those from two recent genome scans, make this the best supported linkage region in BPAD. Further, our data show evidence of a gender effect at this locus with increased sharing predominantly within the male-male pairs. Our scan also provides support for linkage (MLS> or =1.5) at several other regions that have been implicated in meta-analyses of bipolar disorder and/or schizophrenia including 9p21, 10p14-p12 and 18q22. 相似文献
5.
Busby V Goossens S Nowotny P Hamilton G Smemo S Harold D Turic D Jehu L Myers A Womick M Woo D Compton D Doil LM Tacey KM Lau KF Al-Saraj S Killick R Pickering-Brown S Moore P Hollingworth P Archer N Foy C Walter S Lendon C Iwatsubo T Morris JC Norton J Mann D Janssens B Hardy J O'Donovan M Jones L Williams J Holmans P Owen MJ Grupe A Powell J van Hengel J Goate A Van Roy F Lovestone S 《Neuromolecular medicine》2004,5(2):133-146
The gene encoding α-T-catenin, CTNNA3, is positioned within a region on chromosome 10, showing strong evidence of linkage to Alzheimer’s disease (AD), and is therefore
a good positional candidate gene for this disorder. We have demonstrated that α-T-catenin is expressed in human brain, and
like other α-catenins, it inhibits Wnt signaling and is therefore also a functional candidate. We initially genotyped two
single-nucleotide polymorphisms (SNPs) in the gene, in four independent samples comprising over 1200 cases and controls but
failed to detect an association with either SNP. Similarly, we found no evidence for association between CTNNA3 and AD in a sample of subjects showing linkage to chromosome 10, nor were these SNPs associated with Aβ deposition in brain.
To comprehensively screen the gene, we genotyped 30 additional SNPs in a subset of the cases and controls (n>700). None of these SNPs was associated with disease. Although an excellent candidate, we conclude that CTNNA3 is unlikely to account for the AD susceptibility locus on chromosome 10. 相似文献
6.
A polymorphic variation in the interleukin 1A gene increases brain microglial cell activity in Alzheimer's disease 下载免费PDF全文
Hayes A Green EK Pritchard A Harris JM Zhang Y Lambert JC Chartier-Harlin MC Pickering-Brown SM Lendon CL Mann DM 《Journal of neurology, neurosurgery, and psychiatry》2004,75(10):1475-1477
OBJECTIVE: To investigate the impact of possession of the -889 C/T polymorphism of the interleukin 1A gene (IL-1A) and the -511 C/T polymorphism of the interleukin 1B gene (IL-1B) on the extent of neuroinflammation in the brain in Alzheimer's disease (AD), as demonstrated by the degree of microglial cell activity associated with each IL-1A and IL-1B genotype. METHOD: Microglial cell activity within the frontal cortex was determined in 68 patients with necropsy confirmed AD by image analysis as the percentage area of tissue occupied by ferritin immunostained material (microglial cell load). IL-1A, IL-1B, and apolipoprotein E (APOE) genotyping were performed by polymerase chain reaction on DNA extracted from frontal cortex or cerebellum. RESULTS: The microglial cell load was 31% greater in patients with IL-1A T allele, 62% greater with IL-1A TT genotype, but 108% greater with IL-1A TT genotype in combination with APOE epsilon4 allele. No effects on microglial cell load occurred with polymorphisms in IL-1B, or APOE alone. CONCLUSIONS: Polymorphisms within IL-1A influence the degree of brain microglial cell activation, especially in bearers of APOE epsilon4 allele, reinforcing the importance of neuroinflammatory processes in the pathogenesis of AD, and supporting the rationale for treating the disease with inflammation modulating drugs. 相似文献
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Chapuis J Hannequin D Pasquier F Bentham P Brice A Leber I Frebourg T Deleuze JF Cousin E Thaker U Amouyel P Mann D Lendon C Campion D Lambert JC 《Neurobiology of disease》2008,30(1):103-106
The first genome-wide association in Alzheimer's disease (AD) suggested that the GAB2 gene rs2373115 polymorphism may be a strong risk factor in APOE varepsilon4-carriers. We failed to detect an association of rs2373115 with the risk of developing AD in three populations (totalling 1406 controls and 1749 AD cases) whatever the APOE status, even if we observed a slight tendency for an increase of the GG genotype (OR (GG versus GT+TT)=1.3, 95% CI 1.0-1.6, p=0.09) and the G allele frequency (OR=1.3, 95%CI 1.0-1.6, p=0.05) in varepsilon4-carriers. In addition, the rs2373115 did not modulate the extent of tau phosphorylation in the brain of 89 AD cases. The GAB2 gene is at best a minor genetic determinant of AD. 相似文献
9.
Cook LJ Ho LW Taylor AE Brayne C Evans JG Xuereb J Cairns NJ Pritchard A Lemmon H Mann D St Clair D Turic D Hollingworth P Moore PJ Jehu L Archer N Walter S Foy C Edmondson A Powell J Lovestone S Owen MJ Williams J Lendon C Rubinsztein DC 《Neuroscience letters》2004,358(2):142-146
Consistent deficits in the cholinergic system are evident in Alzheimer's disease (AD) patients, including selective loss of alpha4beta2 nicotinic acetylcholine receptors in the brains of AD patients. Knockout mice for the beta2 subunit have impaired neuronal survival in ageing. Accordingly, we have analysed polymorphisms in the genes that encode the alpha4 and beta2 subunits, CHRNA4 and CHRNB2 respectively, for genetic associations with late-onset AD. A significant association for disease was observed for a non-coding polymorphism in CHRNB2 (odds ratio=0.57, 95% confidence interval=0.35-0.95, P=0.024). Replication analysis was performed in two further sample sets. While these did not individually yield significant results, a significant association remained when all samples were pooled (odds ratio=0.70, 95% confidence interval=0.52-0.95, P=0.019). These data suggest that this variant warrants further examination in large case-control series. 相似文献
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