全文获取类型
收费全文 | 316篇 |
免费 | 14篇 |
专业分类
耳鼻咽喉 | 15篇 |
儿科学 | 10篇 |
妇产科学 | 2篇 |
基础医学 | 43篇 |
口腔科学 | 1篇 |
临床医学 | 27篇 |
内科学 | 88篇 |
皮肤病学 | 7篇 |
神经病学 | 25篇 |
特种医学 | 23篇 |
外科学 | 61篇 |
预防医学 | 9篇 |
眼科学 | 5篇 |
药学 | 6篇 |
肿瘤学 | 8篇 |
出版年
2024年 | 1篇 |
2023年 | 6篇 |
2022年 | 2篇 |
2021年 | 5篇 |
2020年 | 4篇 |
2019年 | 5篇 |
2018年 | 6篇 |
2017年 | 4篇 |
2016年 | 3篇 |
2015年 | 10篇 |
2014年 | 7篇 |
2013年 | 24篇 |
2012年 | 16篇 |
2011年 | 17篇 |
2010年 | 11篇 |
2009年 | 7篇 |
2008年 | 17篇 |
2007年 | 20篇 |
2006年 | 18篇 |
2005年 | 21篇 |
2004年 | 19篇 |
2003年 | 13篇 |
2002年 | 20篇 |
2001年 | 7篇 |
2000年 | 6篇 |
1999年 | 5篇 |
1998年 | 3篇 |
1996年 | 1篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1990年 | 2篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 10篇 |
1985年 | 5篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1979年 | 3篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1973年 | 1篇 |
1971年 | 3篇 |
1970年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有330条查询结果,搜索用时 31 毫秒
31.
Joost Lumens Tammo Delhaas Borut Kirn Theo Arts 《Annals of biomedical engineering》2009,37(11):2234-2255
A mathematical model (TriSeg model) of ventricular mechanics incorporating mechanical interaction of the left and right ventricular
free walls and the interventricular septum is presented. Global left and right ventricular pump mechanics were related to
representative myofiber mechanics in the three ventricular walls, satisfying the principle of conservation of energy. The
walls were mechanically coupled satisfying tensile force equilibrium in the junction. Wall sizes and masses were rendered
by adaptation to normalize mechanical myofiber load to physiological standard levels. The TriSeg model was implemented in
the previously published lumped closed-loop CircAdapt model of heart and circulation. Simulation results of cardiac mechanics
and hemodynamics during normal ventricular loading, acute pulmonary hypertension, and chronic pulmonary hypertension (including
load adaptation) agreed with clinical data as obtained in healthy volunteers and pulmonary hypertension patients. In chronic
pulmonary hypertension, the model predicted right ventricular free wall hypertrophy, increased systolic pulmonary flow acceleration,
and increased right ventricular isovolumic contraction and relaxation times. Furthermore, septal curvature decreased linearly
with its transmural pressure difference. In conclusion, the TriSeg model enables realistic simulation of ventricular mechanics
including interaction between left and right ventricular pump mechanics, dynamics of septal geometry, and myofiber mechanics
in the three ventricular walls. 相似文献
32.
CCN3 is a novel endogenous PDGF-regulated inhibitor of glomerular cell proliferation 总被引:1,自引:0,他引:1
van Roeyen CR Eitner F Scholl T Boor P Kunter U Planque N Gröne HJ Bleau AM Perbal B Ostendorf T Floege J 《Kidney international》2008,73(1):86-94
CCN proteins affect cell proliferation, migration, attachment, and differentiation. We identified CCN3 as a suppressed gene following platelet-derived growth factor (PDGF)-BB or -DD stimulation in a cDNA-array analysis of mesangial cells. In vitro growth-arrested mesangial cells overexpressed and secreted CCN3, whereas the addition of the recombinant protein inhibited cell growth. Induction of mesangial cell proliferation by PDGF-BB or the specific PDGF beta-receptor ligand PDGF-DD led to downregulation of CCN3 mRNA, confirming the array study. Specific PDGF alpha-receptor ligands had no effect. CCN3 protein was found in arterial smooth muscle cells, the medullary interstitium, and occasional podocytes in the healthy rat kidney. Glomerular CCN3 was low prior to mesangial proliferation but increased as glomerular cell proliferation subsided during mesangioproliferative glomerulonephritis (GN). Inhibition of PDGF-B in mesangioproliferative disease led to overexpression of glomerular CCN3 mRNA. CCN3 localized mostly to podocytes in human glomeruli, but this expression varied widely in different human glomerulonephritides. Glomerular cell proliferation negatively correlated with CCN3 expression in necrotizing GN. Our study identifies CCN3 as an endogenous inhibitor of mesangial cell growth and a modulator of PDGF-induced mitogenesis. 相似文献
33.
Cumulative trauma disorder (CTD) occurrences peaked in number in 1994 and although decreasing in 1995, still accounted for 62% of all illness cases reported. A CTD Management Evaluation Tool was developed to assist Occupational Safety and Health Compliance Officers (CSHOs) in program evaluation and documentation of the occupational health management component and the need for an ergonomics program. Occupational and environmental health nurses may use the tool not only to reduce and prevent CTD occurrences, but also as a benchmark for program evaluation. 相似文献
34.
The map kinase ERK regulates renal activity of cyclin-dependent kinase 2 in experimental glomerulonephritis. 总被引:1,自引:0,他引:1
Dirk Bokemeyer Darius Panek Masashi Kitahara James M Trzaskos Christa E Müller J?rg Hockemeyer Uta Kunter Peter Boor Jürgen Floege Herbert J Kramer Tammo Ostendorf 《Nephrology, dialysis, transplantation》2007,22(12):3431-3441
BACKGROUND: In vitro, the extracellular signal-regulated kinase (ERK) is an intracellular convergence point of multiple stimuli, which affect the cell cycle. However, the role of ERK in cell cycle regulation in vivo is unknown. METHODS: To address this issue, ERK activity was blocked both in vitro in mesangial cells (MC) and in vivo in experimental glomerulonephritis (GN) by a pharmacological inhibitor (U0126) of the ERK-activating kinase. RESULTS: In stimulated MC, inhibition of ERK reduced cyclin-dependent kinase 2 (CDK2) phosphorylation, CDK2 activity and cyclin E/A expression, whereas downregulation of CDK inhibitor p27(Kip1) expression was inhibited. In vivo, U0126 was given to rats in the acute phase of anti-Thy 1.1 GN. We previously showed that glomerular cell proliferation was reduced by 67% upon treatment with the inhibitor compared to nephritic controls. Now, we detected a significant increase in renal CDK2-activity/phosphorylation in the nephritic controls, that was significantly and dose-dependently reduced by ERK inhibition. CDK2 activation was accompanied by an increase in renal expression of cyclins E/A and the enhanced binding of these cyclins to CDK2 in the nephritic controls. These changes were blunted by U0126 treatment. Finally, we noted an increased expression and CDK2-binding of p27(KIP1) protein in the nephritic controls which was decreased in U0126 treated rats. CONCLUSIONS: Our observations provide the first evidence that ERK is an intracellular regulator of renal CDK2 activity in vivo in a glomerulonephritis model. 相似文献
35.
Tammo Ostendorf An S De Vriese Jürgen Floege 《Nephrology, dialysis, transplantation》2007,22(10):2778-2780
Humanized, anti-vascular endothelial growth factor (VEGF) antibodieslike bevacizumab (Avastin) have been approved by the FDA forsystemic treatment in cancer and local application in age-relatedmacular degeneration [1]. In a recent review and meta-analysisof published clinical trials with bevacizumab, a dose-dependentincrease in the risk for proteinuria and hypertension was documented[2]. The FDA therefore issued warnings concerning the renaltoxicity and thromboembolic events (http://www.fda.gov/cder/drug/InfoSheets/patient/bevacizumabPIS.htm).Preclinical testing of anti-human VEGF agents in the past wasoften difficult, since most of the anti-human VEGF antibodiesfailed to neutralize rodent VEGF-A.
Summary of key findings
In the 27 相似文献
36.
No association of the -2518 MCP-1 A/G promoter polymorphism with incidence and clinical course of IgA nephropathy. 总被引:3,自引:0,他引:3
Oliver M Steinmetz Ulf Panzer Sigrid Harendza Peter R Mertens Tammo Ostendorf Jürgen Floege Udo Helmchen Rolf A K Stahl 《Nephrology, dialysis, transplantation》2004,19(3):596-601
BACKGROUND: The clinical course of IgA nephropathy is highly variable, ranging from complete remission to progression with end-stage renal disease. Although the mechanisms involved in disease progression are not characterized in detail, loss of renal function is positively correlated with mononuclear cell infiltration. In general, chemokines play an important role in the directional recruitment of inflammatory cells. Recently, a polymorphism in the distal 5' regulatory region of the chemokine monocyte chemoattractant protein-1 (MCP-1), which affects gene expression, has been described (A/G at position -2518). The aim of our study was to evaluate a possible association of this polymorphism with disease progression in patients with IgA nephropathy, as well as susceptibility to this form of glomerulonephritis. METHODS: Blood samples from 207 patients with biopsy proven IgA nephropathy and 140 ethnically, age and sex-matched healthy controls were collected and genomic DNA was extracted. MCP-1 -2518 genotype was assessed by PCR, followed by restriction fragment length polymorphism analysis. Genotype distribution between the two groups was compared by chi(2) test. Cumulative renal survival was assessed by Kaplan-Meier plot and log-rank analysis. RESULTS: 111 (53.6%) patients had the MCP-1 -2518 wild-type A/A, 83 (40.1%) were heterozygous for the G allele and 13 (6.3%) patients showed homozygosity. The allelic distribution was not significantly different in the control group of 140 healthy blood donors (P = 0.71). Renal survival analysis of patients did not reveal statistically significant differences in cumulative survival (P = 0.32), median survival time and 5 year survival rate between the wild-type group and carriers of the G allele. Furthermore, the number of infiltrating CD68-positive monocytes/macrophages into the kidneys of patients with IgA nephropathy was not statistically different between the groups. CONCLUSION: Our data indicate that no association exists between the -2518 A/G polymorphism and susceptibility to IgA nephropathy or its clinical course. 相似文献
37.
Dominik Peus MD a; Helmut Jungtäubl ; Sigurd Knaub PhD ; Andreas Leuker ; Klaus Gerecht MD ; Rolf Ostendorf MD ; Wolfgang Meyer-Ingold PhD ; Meinhard Wlaschek PhD ; Thomas Krieg MD ; Thomas Ruzicka MD ; Karin Scharffetter-Kochanek MD 《Wound repair and regeneration》1995,3(3):265-272
Cellular responses to platelet-derived growth factor, which affects all phases of the wound healing process, are dependent on the interaction of the growth factor with its cell surface receptors. Recently, we have shown that the platelet-derived growth factor-receptor was not expressed in uninjured human skin. In acute human wounds healing by secondary intention, both platelet-derived growth factor-receptor subunits were coordinately expressed, whereas no expression was found after reepithelialization at day 47. Even though impaired wound healing may be due to uncoordinated expression or the failure to express platelet-derived growth factor-receptor subunits, little is known regarding their expression in chronic ulcers. We studied the localization of platelet-derived growth factor-receptor expression in chronic venous leg ulcers of 15 patients with a median age of 73 years. Cryostat sections of biopsy specimens were immunostained with the use of antibodies against the alpha- and the beta-platelet-derived growth factor subunits. RNA was extracted from biopsy specimens and subjected to Northern blot analysis with the use of oligolabeled complementary DNA for the platelet-derived growth factor-receptor. Platelet-derived growth factor-receptor alpha- and beta-subunit expression was found in fibroblast-like cells within the wound bed and in cells beneath the epidermis of the wound edge. Platelet-derived growth factor-receptor beta-subunit expression was detected in endothelial cells of the vessels, in the granulation tissue, and the wound edge, whereas platelet-derived growth factor-receptor alpha-subunit was not expressed in endothelial cells of the uninjured skin. This finding suggests that the platelet-derived growth factor alpha-subunit may be involved in vessel formation during tissue repair. Both platelet-derived growth factor-receptor subunits were expressed at the messenger RNA level indicating that the synthesis is at least partly regulated at a pretranslational level. As the cellular responsiveness to growth factors depends on their specific receptors, our finding that both platelet-derived growth factor-receptor subunits are expressed in chronic venous ulcers substantiates the concept of therapeutic trials with recombinant platelet-derived growth factor. 相似文献
38.
B Ostendorf P Dann F Wedekind U Brauckmann J Friemann J Koebke K P Schulitz M Schneider 《The Journal of rheumatology》1999,26(9):1901-1908
OBJECTIVE: To evaluate miniarthroscopy (MA) (needle arthroscopy) of involved joints in rheumatoid arthritis (RA) in the early detection and staging of synovitis and its application in visual guided synovial biopsies. METHODS: 1.0 and 1.9 mm (0 degree/30 degrees) arthroscopes were used in a 2 portal technique. MA performance was developed and evaluated first on hand cadavers (n = 20) and then transferred to metacarpophalangeal (MCP) joints under local anesthesia conditions. Joints of 20 patients with RA with different disease activity and duration were scoped and rated according to scores adapted from arthroscopy of other joints. RESULTS: In 20/20 cases MA provided visualizing and magnification of intraarticular features of MCP joints in RA and allowed grading of synovial alterations, chondromalacia, and bony alterations. Synovial surface changes, thickness, and fibrosis were related to disease duration, as was damage to cartilage and bone. The degree of acute inflammatory reactions like vascularity and hyperemia varied independently of chronic changes; synovial proliferation was reflected to some extent by C-reactive protein. In 2 patients with early RA, synovitis criteria were found macroscopically and histologically. In 18/20 joints, biopsies were taken under visual control; in the other 2, progression of disease (Larsen score >3) limited arthroscopy to 1.0 scope imaging only. Sampling sizes were sufficient for histologic and molecular analysis. CONCLUSION: The developed standardized procedure of MCP arthroscopy is minimally invasive, practicable, and well tolerated by patients, and may allow synovitis monitoring, staging, and biopsy in patients with early as well as chronic arthritis. 相似文献
39.
B Pfalzer H Hamm U Beisiegel P Ostendorf 《The Journal of laboratory and clinical medicine》1992,120(3):483-493
We investigated the lipoproteins and apoproteins in human serum and pleural effusions of different origin: transudates, inflammatory exudates, and malignant exudates. Transudates had a low cholesterol content of 35 +/- 12 mg/dl (mean +/- SD) because of low levels of low-density lipoprotein (LDL) cholesterol--representing 16% of serum levels--whereas inflammatory exudates (cholesterol 92 +/- 26 mg/dl) and malignant exudates (cholesterol 86 +/- 6 mg/dl) exhibited high levels of LDL, with 67% and 69% of serum levels. Apolipoprotein (apo) B level corresponded with LDL and presented with multiple split-products in sodium dodecyl sulfate-polyacrylamide gel electrophoresis in exudative effusions. LDL levels in effusions correlated with serum levels in exudates but did not correlate with those in transudates. In contrast, lipoprotein(a) appeared in all effusions from patients with detectable serum levels. The isoforms were similar as demonstrated by immunoblotting. Differences were found in the composition of the high-density lipoprotein (HDL) fraction: transudates had cholesterol-rich HDL when compared with serum. HDL particles of malignant exudates were poor in cholesterol, and isoelectric focusing demonstrated more sialized apolipoprotein E. A strongly abnormal HDL level with accumulation of cholesterol was found in a long-standing tuberculous effusion. In conclusion, cholesterol in acute effusions is bound to lipoproteins and derived from the blood. The difference in total cholesterol levels between transudates and exudates is based on the lack of LDL in transudates. Transudates show the lipoprotein characteristics of interstitial fluid. Alterations of lipoproteins occur in chronic inflammation and in malignancy with possible de novo synthesis of apolipoprotein E by tumor cells. Lipoprotein(a) accumulates independently from LDL in the pleural space, a finding that supports the view that the physiologic function of lipoprotein(a) is located in the interstitial space. 相似文献
40.
Oleksii Ostras Andrii Kurkevych Lyubomyr Bohuta Tetyana Yalynska Tammo Raad Mark Lewin Illya Yemets 《Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital》2015,42(2):169-171
Pulmonary arteriovenous fistula is a rare disease. To the best of our knowledge, prenatal diagnosis of a fistula between the left pulmonary artery and the left pulmonary vein has not been described in the medical literature. We report a case of the prenatal diagnosis of a left pulmonary artery-to-pulmonary vein fistula, followed by successful neonatal surgical repair. 相似文献