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排序方式: 共有342条查询结果,搜索用时 15 毫秒
11.
Tessa Crompton Susan V. Outram Jennifer Buckland Michael J. Owen 《European journal of immunology》1998,28(6):1859-1866
Mouse mutants lacking expression of the IL-7 receptor (IL-7R) α chain are defective in thymopoiesis. The adult thymus has multiple defects, including reduced cell numbers and proportions of the more mature thymocyte subsets, a complete absence of CD25+ cells and a reduced level of RAG1 and RAG2 expression. We show here that, in contrast to the profound developmental arrest observed in the adult thymus, fetal thymocytes from IL-7Rα−/− mice have normal proportions of all of the major thymocyte subpopulations, including CD25+ thymocytes and the most mature single-positive subsets. Moreover, normal levels of RAG1 and RAG2 were observed. Total thymocyte numbers, however, remained reduced. These data suggest that the IL-7Rα chain is a key regulator of both survival and proliferation during thymocyte development but that it is not essential for the production of T cells during fetal thymopoiesis. 相似文献
12.
Anney RJ Rees MI Bryan E Spurlock G Williams N Norton N Williams H Cardno A Zammit S Jones S Jones G Hoogendoorn B Smith K Hamshere ML Coleman S Guy C O'Donovan MC Owen MJ Buckland PR 《Molecular psychiatry》2002,7(5):493-502
The dopamine D(3) receptor gene (DRD3) is a candidate for a number of psychiatric conditions including schizophrenia, bipolar disorder and alcohol and drug abuse. Previous studies have reported associations between polymorphisms in DRD3 and these disorders, but these findings may have reflected linkage disequilibrium with pathogenic variants that are further upstream. We have isolated and sequenced approximately 9 kb of genomic sequence upstream of the human DRD3 translational start site. Using 5' RACE, we have identified within this region three additional exons and two putative promoter regions which show promoter activity in three different cell lines. A 5' UTR identified only in lymphoblasts is spread over three exons and is 353 bp long. A second 5' UTR, found in adult and fetal brain, lymphocytes, kidney and placenta is spread over two exons and is 516 bp long. A 260-bp sequence within this 9 kb corresponds to a previously reported EST, but corresponding mRNA could not be found in the tissues above. The EST, 5' UTRs and putative promoter regions have been analysed for polymorphisms, revealing 10 single nucleotide polymorphisms, seven of which were tested for association in a large sample of unrelated patients with schizophrenia and matched controls. No associations were observed with schizophrenia. In addition we failed to replicate previous findings of association with homozygosity of the Ser9Gly variant. The results from this study imply that neither the coding nor the regulatory region of DRD3 plays a major role in predisposition to schizophrenia. 相似文献
13.
Buckland JR Manjaly G Violaris N Howlett DC 《The Journal of laryngology and otology》1999,113(11):988-992
We describe the technique of ultrasound-guided 18 gauge (1.2 mm) needle biopsy in 16 patients with parotid gland lesions. This provides material suitable for histological analysis and can be performed quickly and safely under local anaesthesia. Thirteen of the patients had non-diagnostic blind fine-needle aspiration cytology (FNAC) with a 21 gauge (0.8 mm) needle prior to biopsy. Initial ultrasound was found to be superior to clinical examination in 31 per cent of cases. The ultrasound-guided technique provided a diagnostic specimen in 100 per cent of patients and was helpful where FNAC had been inconclusive. There was a diagnostic accuracy of 100 per cent in the patients who underwent subsequent surgery. This method should be considered when FNAC is non-diagnostic and surgical treatment is being considered. It is particularly useful in patients with diffuse enlargement of the gland and does provide a core of material for accurate assessment of tissue architecture. In this series, nine patients avoided unnecessary surgery. 相似文献
14.
W. Buckland 《Journal of urban health》1974,50(7):872-Aug;50(7):872
15.
Bray NJ Jehu L Moskvina V Buxbaum JD Dracheva S Haroutunian V Williams J Buckland PR Owen MJ O'Donovan MC 《Human molecular genetics》2004,13(22):2885-2892
The epsilon4 haplotype of APOE is the only undisputed genetic risk factor for late-onset Alzheimer's disease (LOAD). It has been proposed that at least two other polymorphisms in the promoter of the APOE gene (-219G>T and -491A>T) might also contribute to disease susceptibility, and modulate the impact of structural changes in the ApoE protein, by altering its expression. In order to assess the extent of cis-acting influences on APOE expression in human brain, highly quantitative measures of allele discrimination were applied to cortical RNA from individuals heterozygous for the epsilon alleles. A small, but significant, increase in the expression of epsilon4 allele was observed relative to that of the epsilon3 and epsilon2 alleles (P<0.0001). Similar differences were observed in brain tissue from confirmed LOAD subjects, and between cortical regions BA10 (frontopolar) and BA20 (inferior temporal). Stratification of epsilon4/epsilon3 allelic expression ratios according to heterozygosity for the -219G>T promoter polymorphism revealed significantly lower relative expression of haplotypes containing the -219T allele (P=0.02). Our data indicate that, in human brain, most of the cis-acting variance in APOE expression is accounted for by the epsilon4 haplotype, but there are additional, small, cis-acting influences associated with promoter genotype. 相似文献
16.
The serotonin-2A (HTR2A) receptor is a molecule of particular interest in biological psychiatry, as it is an important target for psychotropic drugs, and altered HTR2A expression has been found in several neuropsychiatric conditions, including depression and schizophrenia. Genetic association has been reported between a synonymous 102T/C polymorphism in the gene encoding HTR2A and a number of clinical phenotypes, including schizophrenia, clozapine response, psychotic symptoms in Alzheimer's disease and certain features of depression. Given that there are no known effects of the 102T/C polymorphism on the structure of the receptor, attention has switched to the possibility that the observations of both altered expression and genetic association point to functional sequence variants that alter expression of the HTR2A gene. Moreover, data have been presented recently suggesting that mRNAs containing the 102T- and C-alleles are differentially expressed. This suggests a direct effect of the variant itself on mRNA levels, or the influence of a distinct regulatory variant, such as the -1438A/G promoter polymorphism, with which it is in perfect linkage disequilibrium. The present study tested this hypothesis by employing a highly accurate quantitative allele- specific primer extension assay to measure the relative expression of brain mRNAs carrying each allele in 23 individuals heterozygous for the 102T/C polymorphism. Comparison between allele ratios derived from genomic DNA and mRNA from several cortical regions revealed that the 102C- and T-alleles are expressed identically. Furthermore, the absence of any interindividual variability in relative mRNA allele ratio suggests that the HTR2A locus is unlikely to contain common polymorphisms or epigenetic modification that alter HTR2A mRNA levels in adult brain, and essentially exclude such phenomena as a potential explanation for the altered expression and genetic associations that have been reported to date. 相似文献
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20.
Yuri V. Bobryshev Dinh Tran Murray C. Killingsworth Michael Buckland Reginald V. N. Lord 《Journal of gastrointestinal surgery》2009,13(3):442-450
Background The development of Barrett’s esophagus is poorly understood, but it has been suggested that cardiac mucosa is a precursor
of intestinal type metaplasia and that inflammation of cardiac mucosa may play a role in the formation of Barrett’s esophagus.
The present study was undertaken to examine the presence and distribution of immune-inflammatory cells in cardiac mucosa,
specifically focusing on dendritic cells because of their importance as regulators of immune reactions.
Material and Methods Endoscopic biopsy specimens were obtained from 12 patients with cardiac mucosa without Barrett’s esophagus or adenocarcinoma
and from 21 patients with Barrett’s esophagus without dysplasia (intestinal metaplasia). According to histology, in nine of
the 21 specimens with Barrett’s esophagus, areas of mucosa composed of cardiac type epithelium-lined glands were present as
well. Immunohistochemical staining and electron microscopy were used to examine immune-inflammatory cells in paraffin-embedded
sections.
Results Immune-inflammatory cells, including T cells, B cells, dendritic cells, macrophages, and mast cells, were present in the connective
tissue matrix that surrounded cardiac type epithelium-lined glands in all patients with cardiac mucosa. Clustering of dendritic
cells with each other and with lymphocytes and the intrusion of dendritic cells between glandular mucus cells were observed.
In the Barrett’s esophagus specimens that contained cardiac type glands, computerized CD83 expression quantitation revealed
that there were more dendritic cells in cardiac mucosa than in intestinal metaplasia.
Conclusion Immune-inflammatory infiltrates containing dendritic cells are consistently present in cardiac mucosa. The finding of a larger
number of dendritic cells in areas of cardiac mucosa in Barrett’s esophagus biopsies suggests that the immune inflammation
of cardiac mucosa might play a role in modifying the local tissue environment to promote the development of specialized intestinal
type metaplasia.
Funding The research was supported by the National Health and Medical Research Council, Cancer Institute NSW, NSW Cancer Council,
and St. Vincent’s Clinic Foundation, Sydney. 相似文献