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31.
M. S. Kipnes P. Hollander K. Fujioka I. Gantz T. Seck N. Erondu Y. Shentu K. Lu S. Suryawanshi M. Chou A. O. Johnson‐Levonas S. B. Heymsfield D. Shapiro K. D. Kaufman J. M. Amatruda 《Diabetes, obesity & metabolism》2010,12(6):517-531
Aim: To evaluate the efficacy and safety of taranabant in overweight and obese patients with type 2 diabetes mellitus (T2DM). Methods: This was a multicenter, double‐blind, randomized, placebo‐controlled study in overweight and obese patients with T2DM (ages ≥ 18 and ≤ 75 years) with a BMI ≥ 27 kg/m2 and ≤ 43 kg/m2 and HbA1c ≥7.0 and ≤ 10.0%, who were either not on an antihyperglycaemic agent or on a stable dose of metformin (≥ 1500 mg/day). After a 2‐week placebo run‐in, patients were randomized to placebo (N = 156) or taranabant 0.5‐mg (N = 155), 1‐mg (N = 157), or 2‐mg (N = 155) once daily for 52 weeks. Primary efficacy endpoints were changes from baseline in body weight (BW) and HbA1c at Week 36, with results at Week 52 being key secondary endpoints. Results: In the all‐patients‐treated population, using a last‐observation‐carried‐forward analysis, reductions in BW were ?2.5, ?3.7, ?4.5 and ?5.1 kg at Week 36 and ?2.4, ?4.0, ?4.6 and ?5.3 kg at Week 52 in the placebo, 0.5‐, 1‐ and 2‐mg groups, respectively (all doses significant vs. placebo at both time points). The proportion of patients who lost ≥ 5 and ≥ 10% of their baseline BW was significantly greater in the 1‐ and 2‐mg groups vs. placebo at Week 36 and all taranabant groups vs. placebo at Week 52. Reductions in HbA1c were ?0.40, ?0.47, ?0.68 and ?0.71% at Week 36 and ?0.30, ?0.43, ?0.65 and ?0.64% at Week 52, in the placebo, 0.5‐, 1‐ and 2‐mg groups, respectively (1‐ and 2‐mg doses significant vs. placebo at both time points). After 52 weeks, the incidences of adverse experiences classified in the gastrointestinal (diarrhoea, nausea, vomiting), nervous system‐related (dizziness, sensory‐related), and psychiatric (irritability, depression‐related) organ systems were numerically higher or statistically significantly higher in all taranabant groups compared with the placebo group. Conclusions: After 36 and 52 weeks, treatment with taranabant at the 1‐ and 2‐mg doses led to clinically significant weight loss and improvement in glycaemic parameters in overweight and obese patients with T2DM that was associated with dose‐related increases in adverse experiences. Based on these data and data from other Phase III clinical studies, it was determined that the overall safety and efficacy profile of taranabant did not support further development for the treatment of obesity. 相似文献
32.
Expression and effect of basic fibroblast growth factor on human cataract lens epithelial cells 总被引:3,自引:0,他引:3
目的 研究碱性成纤维细胞生长因子 (basicfibroblastgrowthfactor,bFGF)在人眼中的表达及对白内障患者人晶体上皮细胞 (humanlensepithelialcells ,HLEC)增殖的影响。方法 取人眼球免疫组化测定bFGF蛋白 ;白内障术中取晶体前囊膜bFGF培养 ,4 8小时后免疫组化染色和JDIAS医用多功能图象分析软件测定增殖细胞核抗原 (proliferatingcellnuclearantigen ,PCNA)阳性面积率。结果 bFGF在晶体及晶体周围组织广泛存在 ;其促白内障患者HLEC增殖作用呈剂量依赖性 ,且与白内障患者年龄呈负相关 (P <0 0 5 )。结论 bFGF促白内障患者术后残留HLEC增殖 ,参与了后发障的形成。 相似文献
33.
34.
腹部手术病人健康教育评价标准的应用研究 总被引:12,自引:6,他引:12
[目的 ]探讨腹部手术病人健康教育评价标准的应用效果。 [方法 ]将 3 3 5例腹部择期手术病人按时间段分为对照组和实验组 ,对照组按常规实施健康教育 ,实验组参照腹部手术病人健康教育评价指标实施健康教育 ,对两组病人进行健康教育效果评价和满意度调查。[结果 ]两组健康教育效果存在统计学意义 (χ2 =3 75 .5 7,P <0 .0 0 1) ;健康教育满意度实验组 (97.65 % )也高于对照组(88.2 5 % )。 [结论 ]腹部手术病人健康教育评价标准为护理管理者提供了健康教育的质量评价指标 ,为临床护士开展高效率的健康教育提供了可参照的工作方法 ,也提高了病人的自我保健意识和健康行为。 相似文献
35.
一次使用性输液器生产厂房洁净度与微气候检测 总被引:1,自引:1,他引:0
检测6家生产一次使用性输液器厂房的洁净度与微气候,其不合格率均较高。应按生产一次使用性输液器要求加以改造 相似文献
36.
Evaluation of Carotid Atherosclerotic Plaque Stability with Contrast-enhanced Ultrasonography 总被引:1,自引:0,他引:1
This study was aimed to evaluate the relationship between carotid atherosclerotic plaque stability and the clinical symptoms in patients with carotid atherosclerotic plaques by using contrast-enhanced ultrasonography. Fifty patients with carotid atherosclerotic plaques were enrolled and examined with contrast-enhanced ultrasonography. The correlation of contrast agent enhancement of the carotid atherosclerotic plaques and the clinical symptoms was analyzed. The results showed that among the 50 patients, plaques were enhanced in the 23 patients with obvious clinical symptoms. In 27 patients without apparent clinical symptoms, plaques were enhanced sparsely in 15 patients and not enhanced in 12 patients. It was suggested that contrast-enhanced ultrasonography could be used for the examination of the microcirculation in carotid atherosclerotic plaques on real-time basis and serve as a new noninvasive approach for the assessment of stability of carotid atherosclerotic plaques. 相似文献
37.
Computer construction and analysis of protein models of the mutant γD-crystallin gene 总被引:3,自引:0,他引:3
Background γD-crystallin plays an important role in human cataract formation. Being highly stable, γD-crystallin proteins are composed of two domains. In this study we constructed and analyzed protein models of the mutant γD-crystallin gene, which caused a special fasciculiform congenital cataract affecting a large Chinese family.Methods γD-crystallin protein structure was predicted by Swiss-Model software using bovine γD-crystallin as a template and Prospect software using human βb2-crystallin as a template. The models were observed with a Swiss-Pdb viewer. Results The mutant γD-crystallin structure predicted by the Swiss-Model software showed that proline23 was an exposed surface residue and P23T change made a decreased hydrogen bond distance between threonine23 and asparagine49. The mutant γD-crystallin structure predicted by the Prospect software showed that the P23T change exerted a significant effect on the protein‘s tertiary structure and yielded hydrogen bonds with aspartic acid21, asparagine24, asparagine49 and serine74. Conclusion The mutant γD-crystallin gene has a significant effect on the protein‘s tertiary structure, supporting that alteration of γ-crystallin plays an important role in human cataract formation. 相似文献
38.
碱性成纤维细胞生长因子在牛晶状体上皮细胞中的表达和调控 总被引:2,自引:0,他引:2
目的 探讨牛晶状体上皮细胞 (BLEC)中碱性成纤维细胞生长因子 (bFGF)的表达和胎牛血清对表达的调控作用 ,推测白内障摘除术后血 房水屏障破坏对bFGF的影响。方法 采用免疫组化法和Westernblot法检测体外培养的BLEC中bFGF的表达 ,以及不同浓度胎牛血清 (0 1%、1 0 %及 10 0 % )作用 2 4h、10 0 %胎牛血清作用不同时间 (4、8、12及 2 4h)对bFGF相对表达量的影响。结果 免疫组化法检测显示绝大部分BLEC胞浆中可见bFGF表达。Westernblot法检测显示BLEC中表达的bFGF相对分子质量为 180 0 0 ;bFGF的表达随胎牛血清浓度的增加而增强 ,差异有显著意义 (P <0 0 5 ) ;随胎牛血清作用时间的延长而增强 ,差异有显著意义 (P <0 0 5 )。结论 BLEC中可见低相对分子质量bFGF的表达 ;胎牛血清可诱导BLEC中bFGF表达 ;白内障摘除术后血 房水屏障的破坏可导致房水中血清浓度改变 ,引起晶状体上皮细胞中bFGF表达增强。 相似文献
39.
Parmeswaran Diagaradjane Jacobo M Orenstein-Cardona Norman E Colón-Casasnovas Amit Deorukhkar Shujun Shentu Norihito Kuno David L Schwartz Juri G Gelovani Sunil Krishnan 《Clinical cancer research》2008,14(3):731-741
PURPOSE: To develop and validate an optical imaging nanoprobe for the discrimination of epidermal growth factor (EGF) receptor (EGFR)-overexpressing tumors from surrounding normal tissues that also expresses EGFR. EXPERIMENTAL DESIGN: Near-infrared (NIR) quantum dots (QD) were coupled to EGF using thiol-maleimide conjugation to create EGF-QD nanoprobes. In vitro binding affinity of these nanoprobes and unconjugated QDs was evaluated in a panel of cell lines, with and without anti-EGFR antibody pretreatment. Serial optical imaging of HCT116 xenograft tumors was done after systemic injection of QD and EGF-QD. RESULTS: EGF-QD showed EGFR-specific binding in vitro. In vivo imaging showed three distinct phases, tumor influx ( approximately 3 min), clearance ( approximately 60 min), and accumulation (1-6 h), of EGF-QD nanoprobes. Both QD and EGF-QD showed comparable nonspecific rapid tumor influx and clearance followed by attainment of an apparent dynamic equilibrium at approximately 60 min. Subsequently (1-6 h), whereas QD concentration gradually decreased in tumors, EGF-QDs progressively accumulated in tumors. On delayed imaging at 24 h, tumor fluorescence decreased to near-baseline levels for both QD and EGF-QD. Ex vivo whole-organ fluorescence, tissue homogenate fluorescence, and confocal microscopic analyses confirmed tumor-specific accumulation of EGF-QD at 4 h. Immunofluorescence images showed diffuse colocalization of EGF-QD fluorescence within EGFR-expressing tumor parenchyma compared with patchy perivascular sequestration of QD. CONCLUSION: These results represent the first pharmacokinetic characterization of a robust EGFR imaging nanoprobe. The measurable contrast enhancement of tumors 4 h after systemic administration of EGF-QD and its subsequent normalization at 24 h imply that this nanoprobe may permit quantifiable and repetitive imaging of EGFR expression. 相似文献
40.
DL111-IT, a non-hormonal contragestional agent, revealed synergistic effects in combination with mifepristone (RU486) in some species. The present study was undertaken to clarify the role of DL111-IT when used alone or plus RU486 on uterine polyamines biosynthesis, histologic alteration of decidual cells, and antifertility activity in rats. The levels of polyamines in pregnant rat uterus were determined by formed benzoyl chloride derivatives of polyamines for RP-HPLC. The results showed that all the treated groups including DL111-IT 2.8 mg. kg(-1). d(-1), RU486 3.0 mg. kg(-1). d(-1), and DL111-IT 0.56 mg. kg(-1). d(-1) plus RU486 0.6 mg. kg(-1). d(-1) caused 100% early pregnancy arrest. Uterine putrescine, spermidine, and spermine levels in comparison with vehicle control were declined significantly from d7 of gestation (1 day after treatment) to d9 or d14 (3 days or 8 days after treatment) by Duncan's multiple range test, and accompanied by histologic alterations, edema, degeneration and dissolution of decidual cells with nuclei indefinite in appearance on d8 of gestation (2 days after treatment). The combined administration at lower doses caused the most injury. The data verified that the decrease in uterine polyamine levels and subsequent decidual cells injuries were the critical role of early pregnancy arrest induced by DL111-IT or RU486. The two compounds used in combination with lower dosages revealed greatly synergistic effects. 相似文献