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排序方式: 共有291条查询结果,搜索用时 15 毫秒
1.
Thrombopoietin receptor (Mpl) expression by megakaryocytes in myeloproliferative disorders 总被引:2,自引:0,他引:2
The thrombopoietin receptor (Mpl) is involved in the pathogenesis of chronic myeloproliferative disorders (CMPD). In this study, we determined Mpl expression by bone marrow cells and megakaryocytes in CMPD by applying laser microdissection, real-time RT-PCR, and immunohistochemistry. Mpl mRNA expression was significantly increased up to 9-fold in total bone marrow cells (p < 0.001) and up to 4-fold in megakaryocytes in chronic myeloproliferative disorders (n = 73) compared to normal controls (n = 26, p = 0.01). Immunohistochemistry revealed heterogeneous Mpl expression by megakaryocytes in CMPD with a stronger accentuation in idiopathic myelofibrosis (IMF) in comparison to polycythaemia vera (PV) and essential thrombocythemia (ET). In addition to megakaryocytes, the erythropoietic lineage was prominently labelled by Mpl antiserum, with considerably stronger staining in polycythaemia vera. We conclude that, in CMPD, megakaryocytes and erythroid cells exhibit increased Mpl expression levels which may contribute to the sustained proliferation of both cell lineages in CMPD. 相似文献
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Systematic characterisation of disease associated balanced chromosome rearrangements by FISH: cytogenetically and genetically anchored YACs identify microdeletions and candidate regions for mental retardation genes 总被引:4,自引:4,他引:4
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Wirth J Nothwang HG van der Maarel S Menzel C Borck G Lopez-Pajares I Brøndum-Nielsen K Tommerup N Bugge M Ropers HH Haaf T 《Journal of medical genetics》1999,36(4):271-278
Disease associated balanced chromosome rearrangements (DBCRs) have been instrumental in the isolation of many disease genes. To facilitate the molecular cytogenetic characterisation of DBCRs, we have generated a set of >1200 non-chimeric, cytogenetically and genetically anchored CEPH YACs, on average one per 3 cM, spaced over the entire human genome. By fluorescence in situ hybridisation (FISH), we have performed a systematic search for YACs spanning translocation breakpoints. Patients with DBCRs and either syndromic or non-syndromic mental retardation (MR) were ascertained through the Mendelian Cytogenetics Network (MCN), a collaborative effort of, at present, 270 cytogenetic laboratories throughout the world. In this pilot study, we have characterised 10 different MR associated chromosome regions delineating candidate regions for MR. Five of these regions are narrowed to breakpoint spanning YACs, three of which are located on chromosomes 13q21, 13q22, and 13q32, respectively, one on chromosome 4p14, and one on 6q25. In two out of six DBCRs, we found cytogenetically cryptic deletions of 3-5 Mb on one or both translocation chromosomes. Thus, cryptic deletions may be an important cause of disease in seemingly balanced chromosome rearrangements that are associated with a disease phenotype. Our region specific FISH probes, which are available to MCN members, can be a powerful tool in clinical cytogenetics and positional cloning. 相似文献
4.
Ekkehard Mehdorn Guntram Kommerell Otmar Meienberg 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》1979,209(3):209-217
Summary The essential disturbance in five patients with vertical nystagmus was an inability to generate smooth pursuit eye movements in the direction of the quick phase of their nystagmus. As the cause of this behavior, the authors suggest an asymmetric impairment of the visual input to the pursuit system. This defect causes a directional preponderance of the pursuit system detectable as a continuous drift off target. The drift is interrupted by refoveating saccades, thus resulting in a vertical nystagmus.
Supported by the Deutsche Forschungsgemeinschaft, SFB 70, B 4 相似文献
Zusammenfassung Fünf Patienten mit Vertikalnystagmus zeigten als wesentliche Störung eine Unfähigkeit, gleitende Folgebewegungen in Richtung der raschen Nystagmusphase auszuführen. Als Ursache dieser Störung nehmen Verff. eine asymmetrische Unterbrechung visueller Zuflüsse zum Folgesystem an. Durch diese Unterbrechung wird das normalerweise bestehende Gleichgewicht im Folgesystem gestört. Es entsteht ein Richtungsüberwiegen im Folgesystem, das sich in einem Abtreiben der Gesichtslinie vom ruhenden Fixierpunkt auswirkt. Dieses Abtreiben wird immer wieder durch Sakkaden korrigiert, so daß ein Nystagmus entsteht.
Supported by the Deutsche Forschungsgemeinschaft, SFB 70, B 4 相似文献
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Borck G Topaloglu AK Korsch E Martiné U Wildhardt G Onenli-Mungan N Yuksel B Aumann U Koch G Ozer G Pfäffle R Scherberg NH Refetoff S Pohlenz J 《The Journal of clinical endocrinology and metabolism》2004,89(8):4136-4141
Isolated TSH deficiency is a rare cause of congenital hypothyroidism. We here report four children from two consanguineous Turkish families with isolated TSH deficiency. Affected children who were screened at newborn age had an unremarkable TSH result and a low serum TSH level at diagnosis. Age at diagnosis and clinical phenotype were variable. All affected children carried an identical homozygous splice site mutation (IVS2 + 5 G--> A) in the TSHbeta gene. This mutation leads to skipping of exon 2 and a loss of the translational start codon without ability to produce a TSH-like protein. However, using specific monoclonal antibodies, we detected a very low concentration of authentic, heterodimeric TSH in serum, indicating the production of a small amount of correctly spliced TSH mRNA. By genotyping all family members with polymorphic markers at the TSHbeta locus, we show that the mutation arose on a common ancestral haplotype in three unrelated Turkish families indicating a founder mutation in the Turkish population. These results suggest that this TSHbeta mutation is among the more common TSHbeta gene mutations and stress the need for a biochemical and molecular genetic workup in children with symptoms suggestive of congenital hypothyroidism, even when the neonatal TSH screening is normal. 相似文献
6.
Schernthaner G 《Atherosclerosis. Supplements》2005,6(3):3-10
Cardiovascular disease is responsible for a large proportion of morbidity and mortality in people with type 2 diabetes, who typically have a clustering of risk factors for coronary heart disease (CHD), including dyslipidaemia. Intensive single-factor interventions to lower blood glucose have not eliminated the increased risk of adverse cardiovascular outcomes in patients with diabetes. In comparison, multifactorial interventions, which include normalizing blood lipids with statins, appear to be more effective in reducing CHD. However, risk reductions in patients with type 2 diabetes are often no better than those seen in people without diabetes, despite the much greater baseline risk in the former group. High-density lipoprotein cholesterol (HDL-C) is an independent risk factor for CHD, but is only minimally improved by statin therapy. Additional interventions aimed at increasing HDL-C can further reduce cardiovascular morbidity and mortality in patients with type 2 diabetes. However, use of fibrates in combination with statins may pose an unacceptable risk of myopathy. Therefore, other strategies for combination therapy are needed to normalize lipids in patients with type 2 diabetes or metabolic syndrome. 相似文献
7.
Beate Vajen Ute Modlich Andrea Schienke Susanne Wolf Britta Skawran Winfried Hofmann Guntram Büsche Hans Kreipe Christopher Baum Irene Santos‐Barriopedro Alejandro Vaquero Brigitte Schlegelberger Cornelia Rudolph 《Genes, chromosomes & cancer》2013,52(4):423-430
Suv39h1 mediates heterochromatin formation in pericentric and telomeric regions by trimethylation of lysine 9 of histone 3 (H3K9me3). Yet, its role in the induction of chromosomal instability is poorly understood. We established a leukemia model by retrovirally expressing Myc in wild‐type and histone methyltransferase Suv39h1‐deficient hematopoietic cells and characterized the resulting leukemias for chromosomal instability. All mice that received cells overexpressing Myc developed myeloid leukemia with a median survival of 44 days posttransplantation. Myc‐overexpressing wild‐type leukemias demonstrated clones with numerical chromosomal aberrations (5/16). In secondary transplantations of these leukemic cells, structural changes, mostly end‐to‐end fusions of chromosomes, appeared (10/12). In contrast, leukemic cells overexpressing Myc with reduced or no Suv39h1 expression had a normal karyotype in primary, secondary, and tertiary transplantations (16/16). Myc‐transduced Suv39h1‐deficient cells showed less critically short telomeres (P < 0.05) compared with Myc‐transduced wild‐type bone marrow cells. Gene expression analysis showed upregulation of genes involved in the alternative lengthening of telomeres (ALT) mechanism. Thus, we hypothesize that loss of Suv39h1 implies activation of the ALT mechanism, in turn ensuring telomere length and stability. Our data show for the first time that Suv39h1 deficiency may prevent chromosomal instability by more efficient telomere stabilization in hematopoietic bone marrow cells overexpressing Myc. © 2013 Wiley Periodicals, Inc. 相似文献
8.
A recurrent synonymous KAT6B mutation causes Say‐Barber‐Biesecker/Young‐Simpson syndrome by inducing aberrant splicing
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