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An earlier study has indicated that a complex recombinant HIV-1 strain dominates the epidemic in Estonia. The objective of this study was to further investigate the molecular epidemiology and genetic structure of HIV-1 in Estonia. Most of the investigated individuals became infected after August 2000 when HIV-1 started to spread rapidly among Estonian intravenous drug users (IDUs). Two viral DNA regions, gag/pol and gp41, were sequenced and subtyped from peripheral blood mononuclear cells or plasma from 141 individuals. Phylogenetic analysis in the gp41 region revealed that the most frequent type of the virus among IDUs was a circulating recombinant form, CRF06_cpx, whereas a few samples showed highest sequence similarity to a subtype A strain circulating in Ukraine and Russia. Likewise, in the gag/pol region, most of the samples were classified as CRF06_cpx, with a few classified as subtype A. In this region, however, 16% of the sequences turned out to be mosaic unique recombinant forms consisting of CRF06_cpx and subtype A. At least 9 mosaic forms were identified, each with distinct patterns of multiple crossover. To characterize Estonian CRF06_cpx as well as recombinant isolates in more detail, 4 near-full-length HIV-1 genomes were sequenced.  相似文献   
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OBJECTIVE: HIV accessory protein Nef is expressed early in the infectious cycle of the virus and has been shown to be an effective immunogen in humoral and cellular immune responses. We have used two different self-replicating pBN vectors and one non-replicating pCGal2 derived (pCG) vector expressing HIV-1 Nef in DNA immunisation of mice in order to determine their efficiency in raising humoral and cellular immune responses. DESIGN AND METHODS: The expression of Nef by the three plasmids was tested by transfections into COS-1 cells. Balb/c mice were immunised with the pBN-NEF and pCGE2-NEF constructs using gold particle bombardment. Immunoblotting and immunocytochemistry were used to detect in vitro expression of Nef. 51Cr release assay, ELISA and immunoblotting were used to detect cellular and humoral immune responses in immunised mice. RESULTS: Efficient in vitro expression of Nef was detected in pBN and pCGE2-NEF transfected cells, in pBN-NEF transfected cells the expression lasting up to three weeks. Anti-Nef antibodies in sera of 13 of 16 pBN-NEF immunised mice were detected within four weeks after the last immunisation, whereas only 2 of 12 pCGE2-NEF immunised mice had very weak anti-Nef antibodies. Twelve of the pBN-NEF immunised mice (75%) and 6 the pCGE2-NEF immunised mice (50%) showed Nef-specific cytotoxic T lymphocyte (CTL) responses within four weeks. CONCLUSIONS: We conclude that the three eukaryotic expression vectors tested are capable of inducing a cell mediated immune response towards HIV-1 Nef and should be considered as part of a genetic HIV vaccine.  相似文献   
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With increasing duration of swimming exercise the heart becomes less sensitive to ischemia, as evaluated by the rate of development of ischemic contracture immediately after the exertion. This delay in the development of ischemic contracture was apparently due to metabolic changes directed to decrease the heart energy consumption in conditions where the capacity for glycolytic ATP production was decreased. A decrease in: 1) the amount of rapidly exchangeable Ca2+, which is bound to anionic sites on the sarcolemmal membrane and 2) the myofibrillar Ca2+ sensitivity seems to play an important role. Regular swimming exercise, which is characterized by a significant cardiac hypertrophy and enhanced heart glycogen content, increased the sensitivity of energy mobilizing processes to catecholamine action. These changes accelerated ATP depletion and the development of an irreversible injury when the heart was made ischemic after catecholamine stimulation. Obtained results together with data from literature underline the importance of regular testing of cardiac function, including echocardiography, in young sportsmen undergoing high-intensity training.  相似文献   
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We report on a de novo 17q21.33 microdeletion, 1.8 Mb in size, detected in a patient with mild intellectual disability, growth retardation, poor weight gain, microcephaly, long face, large beaked nose, thick lower lip, micrognathia and other dysmorphic features. The deletion was detected by whole-genome genotyping BeadChip assay and involves the genomic region between 45,682,246 and 47,544,816 bp on chromosome 17. Among the 24 RefSeq genes included in this deletion are the CA10 and CACNA1G genes that are involved in brain development and neurological processes. A possible candidate gene for the prenatal and postnatal growth retardation is the CHAD gene, which product chondroadherin is a cartilage protein with cell binding properties. These three genes may be responsible for the patient's phenotype.  相似文献   
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Summary The effect of different training regimes (three programmes of both swimming and running exercise) on the heart hypertrophy index and some biochemical indices was evaluated and compared individually with the sensitivity of the corresponding heart to ischaemia in order to elucidate the significance of training intensity and observed changes in the development of heart ischaemic injury. The sensitivity of the heart to ischaemia, evaluated by the rate of development of ischaemic contracture 48 h after completing the exercise programme, increased in parallel with an increase in the heart hypertrophy index. Experiments with different swimming programmes showed that the extent of cardiac hypertrophy increased together with an increase in the duration of everyday swimming bouts. Hypertrophied hearts from trained rats were characterized by greater mobilization of glycogen and increased incorporation of 32P into ATP when investigated 10 min after isoprenaline administration. During total ischaemia the development of ischaemic contracture was accelerated in catecholamine-stimulated trained hearts due to more rapid hydrolysis of ATP compared with that in the hearts from sedentary animals. It is suggested that the observed difference between hearts from sedentary and trained animals is, at least partially, connected with the higher sensitivity of myofibrils to Ca2+ in trained hearts.  相似文献   
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The increasing use of whole-genome array screening has revealed the important role of DNA copy-number variations in the pathogenesis of neurodevelopmental disorders and several recurrent genomic disorders have been defined during recent years. However, some variants considered to be pathogenic have also been observed in phenotypically normal individuals. This underlines the importance of further characterization of genomic variants with potentially variable expressivity in both patient and general population cohorts to clarify their phenotypic consequence. In this study whole-genome SNP arrays were used to investigate genomic rearrangements in 77 Estonian families with idiopathic mental retardation. In addition to this family-based approach, phenotype and genotype data from a cohort of 1000 individuals in the general population were used for accurate interpretation of aberrations found in mental retardation patients. Relevant structural aberrations were detected in 18 of the families analyzed (23%). Fifteen of those were in genomic regions where clinical significance has previously been established. In 3 families, 4 novel aberrations associated with intellectual disability were detected in chromosome regions 2p25.1-p24.3, 3p12.1-p11.2, 7p21.2-p21.1 and Xq28. Carriers of imbalances in 15q13.3, 16p11.2 and Xp22.31 were identified among reference individuals, affirming the variable phenotypic consequence of rare variants in some genomic regions considered as pathogenic.  相似文献   
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Post-mortem analysis with castangiography was performed on 54 patients who died within 30 days of coronary artery bypass surgery. Myocardial failure was the cause of 85% of the deaths. There were 215 coronary anastomoses (4.0 +/- 1.1/patient), 24% of which were non-functioning. Most of the occlusions were due to various technical failures. The most striking features were 1) high occlusion rate (25%) in sequential vein grafts and 2) disastrous complications of coronary endarterectomies. Compared with preoperative angiographic data, only 15 (28%) of the 54 patients were found to have 'complete' revascularization, with patent grafts and all stenosed coronary arteries bypassed. The need for recognition and avoidance of technical complications is stressed: Failures of surgical technique constitute a major risk factor in coronary artery surgery.  相似文献   
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Only eight cases involving deletions of chromosome 17 in the region q22-q24 have been reported previously. We describe an additional case, a 7-year-old boy with profound mental retardation, severe microcephaly, facial dysmorphism, symphalangism, contractures of large joints, hyperopia, strabismus, bilateral conductive hearing loss, genital abnormality, psoriasis vulgaris and tracheo-esophageal fistula. Analysis with whole-genome SNP genotyping assay detected a 5.9 Mb deletion in chromosome band 17q22-q23.2 with breakpoints between 48,200,000-48,300,000 bp and 54,200,000-54,300,000 bp (according to NCBI 36). The aberration was confirmed by real-time quantitative PCR analysis. Haploinsufficiency of NOG gene has been implicated in the development of conductive hearing loss, skeletal anomalies including symphalangism, contractures of joints, and hyperopia in our patient and may also contribute to the development of tracheo-esophageal fistula and/or esophageal atresia.  相似文献   
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