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1.

Background

Cranioplasty is a surgical procedure used to treat a bone defect or deformity in the skull. To date, there is little consensus on the standard-of-care for graft materials used in such a procedure. Graft materials must have sufficient mechanical strength to protect the underlying brain as well as the ability to integrate and support new bone growth. Also, the ideal graft material should be individually customized to the contours of the defect to ensure a suitable aesthetic outcome for the patient.

Purpose

Customized 3D-printed scaffolds comprising of polycaprolactone-β-tricalcium phosphate (PCL-TCP) have been developed with mechanical properties suitable for cranioplasty. Osteostimulation of PCL-TCP was enhanced through the addition of a bone matrix-mimicking heparan sulphate glycosaminoglycan (HS3) with increased affinity for bone morphogenetic protein-2 (BMP-2). Efficacy of this PCL-TCP/HS3 combination device was assessed in a rat critical-sized calvarial defect model.

Method

Critical-sized defects (5 mm) were created in both parietal bones of 19 Sprague Dawley rats (Male, 450–550 g). Each cranial defect was randomly assigned to 1 of 4 treatment groups: (1) A control group consisting of PCL-TCP/Fibrin alone (n = 5); (2) PCL-TCP/Fibrin-HSft (30 μg) (n = 6) (HSft is the flow-through during HS3 isolation that has reduced affinity for BMP-2); (3) PCL-TCP/Fibrin-HS3 (5 μg) (n = 6); (4) PCL-TCP/Fibrin-HS3 (30 μg) (n = 6). Scaffold integration and bone formation was evaluated 12-weeks post implantation by μCT and histology.

Results

Treatment with PCL-TCP/Fibrin alone (control) resulted in 23.7% ± 1.55% (BV/TV) of the calvarial defect being filled with new bone, a result similar to treatment with PCL-TCP/Fibrin scaffolds containing either HSft or HS3 (5 μg). At increased amounts of HS3 (30 μg), enhanced bone formation was evident (BV/TV = 38.6% ± 9.38%), a result 1.6-fold higher than control. Further assessment by 2D μCT and histology confirmed the presence of enhanced bone formation and scaffold integration with surrounding host bone only when scaffolds contained sufficient bone matrix-mimicking HS3.

Conclusion

Enhancing the biomimicry of devices using a heparan sulphate with increased affinity to BMP-2 can serve to improve the performance of PCL-TCP scaffolds and provides a suitable treatment for cranioplasty.  相似文献   
2.
3.

Objectives

To evaluate the effects of conjugated equine estrogens (CE) alone or in combination with medroxyprogesterone acetate (MPA) on glycosaminoglycans (GAGs) in the cervix and horns of the rat uterus.

Study design

Thirty days after ovariectomy, adult rats were randomly divided into four groups: GI, control (treated with drug vehicle); GII, CE (50 μg/kg per day); GIII, MPA (0.2 mg/kg per day), and GIV, CE + MPA (doses as in GII and GIII). Drugs and vehicle were given by gavage during 28 days. Afterwards the animals were anesthetized, the cervix and uterine horns were dissected out and the middle portion fixed in 10% formaldehyde solution; other portions were fixed in acetone for histological examination and glycosaminoglycan quantification, respectively. Agarose gel electrophoresis was used for sulfated GAG analyses, and hyaluronic acid was assayed with an ELISA-like method. Statistical analysis was done by the Student's t test and the Tukey–Kramer test (P < 0.05).

Results

The cervix and uterine horn structures presented signs of atrophy in the control group (GI). The other groups, mainly groups III and IV, had histological aspects of proliferation. In all groups the concentration of sulfated GAGs (especially dermatan sulfate) was higher than that of non-sulfated GAGs, both in cervix and in uterine horns. Estrogens increased sulfated GAG concentration at the cervix and the horn, whereas in uterine horns the amounts of sulfated GAGs were decreased after estrogens plus MPA treatment. The concentration of hyaluronic acid in uterine horns was higher than in cervices.

Conclusions

The profiling and amounts of glycosaminoglycans in the two portions of the rat uterus are uneven. Dermatan sulfate occurs in higher concentrations in both cervix and uterine horns. Sulfated GAGs in rat cervix were increased by estrogens plus MPA, but were decreased by MPA alone in uterine horns.  相似文献   
4.
BACKGROUND: Oxidative stress has emerged as an invariable feature of calculogenesis, the process of stone formation. The cytoprotective action of low molecular weight heparin (LMWH) in calcium oxalate-induced oxidative renal injury in experimental calculogenesis was studied. METHODS: A renal membrane injury model involving gentamicin (40 mg/kg body weight) and 2% ammonium oxalate was used. Rats induced with gentamicin and ammonium oxalate were investigated for any impairment of cellular redox status as revealed by renal superoxide dismutase, catalase, glutathione peroxidase, xanthine oxidase activities and glutathione, ascorbate levels. In renal membrane protein activities such as aminotransferases in kidney and lactate dehydrogenase, total protein in urine of rats rendered lithogenic were assessed and compared with healthy vehicle-treated controls. The biochemical index of tissue lipid peroxidation was assessed in terms of malondialdehyde formation. LMWH was co-administered (250 microg/kg body weight) to gentamicin- and ammonium oxalate-dosed rats. RESULTS: The extent of oxidative damage was indicated by the increased lipid peroxidation in the renal tissues of gentamicin- and ammonium oxalate-administered groups. The decline in the antioxidative status of the stone forming kidneys further confirmed the oxidative stress to renal cells. The extensive nephritic damage in the form of proteinuria was quite evident and the injured status of the tissue was reflected in the significant alterations of the few membrane associated enzyme levels in urine and the kidney. LMWH restricted all the cyto-oxidative ill effects of ammonium oxalate and gentamicin. CONCLUSION: Low molecular weight heparin has antioxidant potential in countering the oxalate/calcium oxalate-mediated oxidative challenge in the experimental lithogenic model.  相似文献   
5.
目的:研究刺参糖胺聚糖对HepG2.2.15细胞HBsAg和HBeAg的抑制作用。方法:培养中的HepG2.2.15细胞可持续分泌HBV。用MTT法检测药物的细胞毒性,用ELISA法检测培养上清中的HBsAg和HBeAg。结果:刺参糖胺聚糖对HepG2.2.15细胞HBsAg和HBeAg的抑制作用存在时间和浓度依赖性。给予4种不同浓度的刺参糖胺聚糖作用3天后,8mg/ml、4mg/ml、2mg/ml组能明显抑制HBsAg和HBeAg的分泌(P<0.05);经药物处理6天后,对细胞外HBsAg和HBeAg分泌的抑制率呈显著差异(P<0.01)。结论:刺参糖胺聚糖具有一定的抗HBV活性。  相似文献   
6.
Plasma chondroitin sulfate (CS) amount and charge density were determined in 45 healthy volunteers (control group), 45 pseudoxanthoma elasticum (PXE)-affected patients and 19 healthy carriers by using fluorophore-assisted carbohydrate electrophoresis (FACE) and HPLC equipped with postcolumn derivatization and fluorescence detection. The mean values of CS amount were 4.9 ± 1.21 for volunteers, 4.7 ± 1.40 for PXE subjects and 4.4 ± 1.44 for the carriers. No significant differences were found for the three human subjects groups. On the contrary, by considering the age of normal volunteers, a significant increase of plasma CS amount was measured. In fact, the volunteers aging from 17 to 40 years (mean 32.1) showed a CS concentration of 4.3 ± 1.30 while the group ranging from 50 to 74 years (mean 56.9) had a value of 5.6 ± 1.16 with a significant increase of + 30.2%. The same significant increase in CS plasma content with increasing age was measured for PXE-affected and healthy carriers group.

Extracted plasma CS was evaluated for the main two unsaturated disaccharides, non-sulfated and 4-monosulfated, and the charge density determined. The mean values were 0.54 ± 0.13 for volunteers, 0.60 ± 0.15 for PXE subjects and 0.50 ± 0.15 for the carriers. A significant increase of + 11.1% was found between the PXE patients and healthy human group but no differences were calculated between the control group and the carriers. Furthermore, besides a CS amount, the volunteers aging from 17 to 40 years (mean 32.1) showed a charge density of 0.53 ± 0.14 while the group ranging from 50 to 74 years (mean 56.9) had a value of 0.58 ± 0.17 with a significant increase of + 9.4%. The same trend was measured for the healthy carriers group. The CS charge density of PXE-affected subjects was found to increase significantly more than healthy controls depending on the age. In fact, the PXE patients aging from 10 to 40 years (mean 29.3) showed a charge density of 0.56 ± 0.14 while the group ranging from 50 to 74 years (mean 58.6) had a value of 0.67 ± 0.11 with a significant increase of + 19.6%. Furthermore, the group of PXE-affected subjects ranging from 50 to 74 years (mean 58.6) showed a significant increase of 15.5% in comparison with the group matched for age (mean 56.9) of healthy volunteers.  相似文献   

7.

Background

Autologous chondrocyte implantation (ACI) has been used to treat cartilage defects in thousands of patients worldwide with good clinical effectiveness 10–20 years after implantation. Information concerning the quality of the repair cartilage is still limited because biopsies are small and rare. Glycosaminoglycan structure influences physiological function and is likely to be important in the long term stability of the repair tissue. The aim of this study was to assess glycosaminoglycans in ACI tissue over a two year period.

Methods

Biopsies were taken from one patient (25 years old) at 12 months and 20 months post-ACI-treatment and from three normal cadavers (21, 22 and 25 years old). Fluorophore-assisted carbohydrate electrophoresis (FACE) was used to quantitatively assess the individual glycosaminoglycans.

Results

At 12 months the ACI biopsy had 40% less hyaluronan than the age-matched cadaveric biopsies but by 20 months the ACI biopsy had the same amount of hyaluronan as the controls. Both the 12 and 20 month ACI biopsies had less chondroitin sulphate disaccharides and shorter chondroitin sulphate chains than the age-matched cadaveric biopsies. However, chondroitin sulphate chain length doubled as the ACI repair tissue matured at 12 months (3913 Da ± 464) and 20 months (6923 Da ± 711) and there was less keratan sulphate as compared to the controls.

Conclusions

Although the glycosaminoglycan composition of the repair tissue is not identical to mature articular cartilage its quality continues to improve with time.  相似文献   
8.
目的研究血清硫酸粘多糖片段(sulfateglycosaminoglycanfragments,SGF)和肿瘤相关物质群(tumorsuppliedgroupoffactors,TSGF)联合检测对诊断非小细胞肺癌(nonsmallcelllungcancer,NSCLC)的应用价值。方法选择2001年5月至2004年5月在广东省肇庆市第一人民医院住院并经病理组织细胞学检查证实的NSCLC患者64例作为实验组,小细胞肺癌16例、肺部良性疾病62例、健康体检者104例作为对照组。采用胶乳凝集法和比色法,联合检测NSCLC实验组及各对照组血清SGF和TSGF。结果利用ROC曲线确立67U/L为血清TSGF诊断肺癌的最佳界限值。早期NSCLC组与对照组之间SGF、TSGF、SGF+TSGF、SGF/TSGF的阳性率具有显著性差异。血清SGF和TSGF并联检测NSCLC患者的灵敏度、特异性、阳性预测值(positivepredictivevalue,PPV)、阳性似然比(positivelikeli-hoodratio,+LR)、阴性似然比(negativelikelihoodratio,-LR)和准确度分别为95.30%、87.80%、55.50%、7.81、0.05和78.90%;串联检测NSCLC患者的灵敏度、特异性、PPV、+LR、-LR和准确度分别为88.70%、98.90%、95.80%、80.60、0.11和91.90%。NSCLC组与对照组SGF、TSGF有显著性差异(χ2=117.48,P<0.01),各对照组之间无显著性差异(χ2=2.17,P>0.05)。结论血清SGF和TSGF联合检测对协助诊断和鉴别诊断NSCLC有十分重要的应用价值。  相似文献   
9.
Aims/hypothesis Retention of atherogenic lipoproteins in the artery wall by proteoglycans is a key step in the development of atherosclerosis. Thiazolidinediones have been shown to reduce atherosclerosis in mouse models. The aim of this study was to determine whether thiazolidinediones modify vascular proteoglycan synthesis in a way that decreases LDL binding.Methods Primate aortic smooth muscle cells were exposed to troglitazone or rosiglitazone, or no stimulus at all for a 24-hour steady-state labelling period. Sulphate incorporation, size and LDL binding affinity of proteoglycans were determined. Proteoglycans secreted by cells in the presence or absence of troglitazone were separated into large and small classes by size exclusion chromatography, and LDL binding affinity was determined.Results Proteoglycans synthesised by cells exposed to troglitazone or rosiglitazone were smaller, with decreased sulphate incorporation and decreased LDL binding affinity. However, troglitazone had a greater effect than rosiglitazone. Troglitazone reduced the LDL binding affinities of both the large and small proteoglycans compared with control. The binding differences persisted when glycosaminoglycan chains released from proteoglycans were incubated with LDL, indicating that troglitazone affects the glycosaminoglycan synthetic machinery of these cells.Conclusions/interpretation Thiazolidinediones decrease the LDL binding affinity of the proteoglycans synthesised by primate aortic smooth muscle cells. This could, in part, account for the reduced atherosclerosis observed in animal models.Abbreviations PPAR peroxisome proliferator-activated receptor - Kd binding constantPresented in part at the 3rd Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology, Salt Lake City, Utah, USA, 6 April 2002  相似文献   
10.
目的:观察舒洛地特对2型糖尿病早期肾病的治疗作用。方法:144例不伴高血压的2型糖尿病早期肾病患者,代谢控制稳定后,原糖尿病治疗方案不变,随机分为常规治疗组、舒洛地特治疗组、苯那普利治疗组及舒洛地特+苯那普利治疗组。观察治疗前、治疗4周、治疗12周,尿白蛋白/尿肌酐(ACR)的变化,同时观察空腹血糖、糖化血红蛋白、血总胆固醇、血甘油三酯、血肌酐、纤维蛋白原的变化。结果:除常规治疗组外,其他三组治疗12周前后的ACR比较均有统计学差异(P〈0.01)。治疗12周后,舒洛地特治疗组、苯那普利治疗组、舒洛地特+苯那普利治疗组与常规治疗12周后相比,ACR下降有统计学差异(P〈0.01),但3组间治疗后12周的差异无统计学意义(P〉0.05)。结论:舒洛地特能减少2型糖尿病早期肾病的ACR,延缓肾病的进展,是一种新的治疗糖尿病肾病的途径。  相似文献   
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