首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   629篇
  国内免费   1篇
  完全免费   41篇
  基础医学   671篇
  2022年   5篇
  2021年   12篇
  2020年   5篇
  2019年   34篇
  2018年   30篇
  2017年   31篇
  2016年   40篇
  2015年   27篇
  2014年   44篇
  2013年   71篇
  2012年   31篇
  2011年   33篇
  2010年   22篇
  2009年   30篇
  2008年   31篇
  2007年   31篇
  2006年   26篇
  2005年   24篇
  2004年   14篇
  2003年   18篇
  2002年   17篇
  2001年   11篇
  2000年   8篇
  1999年   11篇
  1998年   5篇
  1997年   5篇
  1996年   5篇
  1995年   1篇
  1994年   6篇
  1993年   6篇
  1992年   3篇
  1990年   2篇
  1989年   2篇
  1988年   2篇
  1987年   1篇
  1986年   8篇
  1985年   5篇
  1984年   3篇
  1983年   4篇
  1982年   1篇
  1981年   1篇
  1980年   2篇
  1979年   1篇
  1978年   1篇
  1973年   1篇
排序方式: 共有671条查询结果,搜索用时 348 毫秒
1.
生物材料有效性和安全性评价的现状与趋势   总被引:30,自引:2,他引:28  
对生物材料进行有效性和安全性评价是生物材料进入临床前的关键环节。从细胞和组织的水平,利用形态学的检测方法观察材料与机体短期和长期的互作关系是以往评价生物材料的主要内容和手段。新型生物材料近年来迅猛发展,材料的组成、形态、植入部位及用途日趋复杂,对材料的评价相应提出了更高的要求。发展快速、特异、评价体系至关重要。体外实验因操作可控性强,影响因素单一,重复性好而得到大力的发展,通过体内-体外实验的相关分析有望部分替体内实验。近交大动物的开发为生物材料的体内评价更接近人体的真实反应提供了新的契机。近几年来,大量分子生物学的先进检测手段的应用生物材料的评价向细胞和分子水平迈进。TR-PCR、核酸/蛋白杂交技术可以从分子的层面寻找材料和机体互作的重要的分子标记,而显微探测技术(如CONFUCAL)等的应用通过对图像的三维重建而达到对材料-细胞、材料-组织、细胞-组织相互作用清晰而透彻的观察。总之。三“R”原则(replace refine reduce)即发展体外实验;采用灵敏、特异、先进的检测手段;优化并减少实验动物数量,建立材料对分子、细胞、机体互作的系统性评价是生物材料评价的发展趋势和最终目的。  相似文献
2.
Options for the control of emerging and reemerging H5N1 influenza viruses include improvements in biosecurity and the use of inactivated vaccines. Commercially available H5N2 influenza vaccine prevents disease signs and reduces virus load but does not completely prevent virus shedding after challenge with H5N1 virus. By using reverse genetics, we prepared an H5N3 vaccine whose hemagglutinin is 99.6% homologous to that of A/CK/HK/86.3/02 (H5N1). We used the internal genes of A/PR/8/34 and the H5 of A/Goose/HK/437.4/99 (H5N1) after deletion of basic amino acids from its connecting peptide region. The resulting virus was not lethal to chicken embryos and grew to high HA titers in eggs, allowing preparation of HA protein-standardized vaccine in unconcentrated allantoic fluid. The N3 neuraminidase, derived from A/Duck/Germany/1215/73 (H2N3), permitted discrimination between vaccinated and naturally infected birds. The virus construct failed to replicate in quail and chickens. Similar to parental A/PR/8/34 (H1N1), it replicated in mice and ferrets and spread to the brains of mice; therefore, it should not be used as a live-attenuated vaccine. The H5N3 vaccine, at doses of 1.2 microg HA, induced HI antibodies in chickens and prevented death, signs of disease, and markedly reduced virus shedding after challenge with A/CK/HK/86.3/02 (H5N1) but did not provide sterilizing immunity. Thus, reverse genetics allows the inexpensive preparation of standardized, efficacious H5N3 poultry vaccines that may also reduce the reemergence of H5N1 genotypes.  相似文献
3.
壳聚糖棒材的组织相容性和安全性评价   总被引:15,自引:1,他引:14  
生物降解内固定材料要求有良好的生物相容性,我们对壳聚糖棒进行了一系列体外和体内的生物学实验,包括热源反应、皮内注射、皮肤致敏实验、全身过鳘实验,眼结膜角膜实验,皮下埋植急性实验,经口毒性实验,经静脉注射实验、溶血实验、降压物质实验、微核实验,皮下和骨内埋植实验,结果表明:壳聚糖棒有良好物生物相容性和安全性。在皮下和骨内埋早期,壳聚糖棒周围可出现异物反应,埋植后三个月异物反应消失。这种异物反应在PG  相似文献
4.
The pharmacologic profile of desloratadine: a review   总被引:13,自引:1,他引:12  
B. M. Henz 《Allergy》2001,56(S65):7-13
Desloratadine is a new agent for the treatment of diseases such as seasonal allergic rhinitis and chronic urticaria. The pharmacologic profile of desloratadine offers particular benefits in terms of histamine H1-receptor binding potency and H1 selectivity. Desloratadine has a half-life of 21–24 h, permitting once-daily dosing. No specific cautions are required with respect to administration in renal or hepatic failure, and food or grapefruit juice have no effect on the pharmacologic parameters. No clinically relevant racial or sex variations in the disposition of desloratadine have been noted. In combination with the cytochrome P450 inhibitors, ketoconazole and erythromycin, the AUC and Cmax of desloratadine were increased to a small extent, but no clinically relevant drug accumulation occurred. With high-dose treatment (45 mg/day for 10 days), no significant adverse events were observed, despite the sustained elevation of plasma desloratadine levels. Specifically, desloratadine had no effects on the corrected QT interval (QTc) when administered alone, at high dose, or in combination with ketoconazole or erythromycin. Preclinical studies also show that desloratadine does not interfere with HERG channels or cardiac conduction parameters even at high dose. Desloratadine is nonsedating and free of antimuscarinic/anticholinergic effects in preclinical and clinical studies. Novel antiallergic and anti-inflammatory effects have also been noted with desloratadine, a fact which may be relevant to its clinical efficacy.  相似文献
5.
A. Sabbah  S. Hassoun  J. Le  Sellin  C. Andre  H. Sicard 《Allergy》1994,49(5):309-313
Fifty-eight patients with well-documented history of seasonal rhinoconjunctivitis caused by grass pollens were allocated randomly on a double-blind basis to receive either sublingual therapy with a solution of purified, standardized allergen preparation (Stallergenes) or a matched placebo for 17 weeks. The assessment of the effect of oral immunotherapy, done with drops of five-grass allergen extract, was on the clinical symptoms and on the medication score of the authorized rescue treatments. The actively treated patients had significantly (P<0.05 to P<0.01) fewer symptoms of rhinitis (sneezing and rhinorrhea) and of conjunctivitis (redness and tears) during the pollen season than the placebo group. Consumption of nasal solution of sodium cromoglycate and of betamethasone and dexchlorpheniramine was significantly less in the desensitized group (P<0.01). Side-effects were negligible. This study concludes that perlingual immunotherapy with grass pollen extract in grass-pollen-sensitive seasonal hay fever and conjunctivitis patients is effective, easy to perform, inexpensive, and safe.  相似文献
6.
BACKGROUND: The age below 5 years is considered a prudential limit for immunotherapy in view of the possible severity of side-effects. Sublingual immunotherapy (SLIT) seems to be safe, but no study in very young children is available. We performed a safety post-marketing surveillance study in children below 5 years. METHODS: Children aged 3-5 years with respiratory allergy receiving SLIT were followed-up for at least 2 years. A diary card for side-effects was filled by parents at each dose given. Local and systemic side-effects were graded as: mild (no intervention, no dose adjustment), moderate (medical treatment and/or dose reduction), severe (life-threatening/hospitalization/emergency care). The comparative safety of different allergens and regimens was also assessed. RESULTS: One hundred and twenty-six children (mean age 4.2 years, 67 male) were included. Seventy-six (60%) had rhinitis with asthma, 34 (27%) rhinitis only and 16 (13%) only asthma. Immunotherapy was prescribed for mites (62%), grasses (22.2%), Parietaria (11.9%), Alternaria (2.4%) and olive (1.5%). Eighteen children underwent an accelerated build-up. The total number of doses was about 39,000. Nine side-effects were reported in seven children (5.6% patients and 0.2/1000 doses). Two episodes of oral itching and one of abdominal pain were mild. Six gastrointestinal side-effects were controlled by reducing the dose. All side-effects occurred during up-dosing phase. No difference in terms of safety among the allergens used was observed. CONCLUSION: SLIT is safe also in children under the age of 5 years.  相似文献
7.
Oligodeoxynucleotides (ODN) containing CpG motifs mimic the ability of microbial DNA to activate the innate immune system. The resultant response limits the early spread of infectious organisms while promoting the development of adaptive immunity. CpG ODN show promise as vaccine adjuvants and in the treatment of asthma, allergy, infection, and cancer. Due to evolutionary divergence in CpG recognition between species, CpG ODN that are most active in rodents are poorly immunostimulatory in primates. Thus, evidence that CpG ODN have therapeutic activity in mice must be confirmed in primates. Two distinct types of CpG ODN were identified that stimulate primate PBMC. D-type ODN trigger plasmacytoid DC to secrete IFNalpha, monocytes to mature into functionally active DC, and NK cells to secrete IFNgamma. K-type ODN stimulate B cells and monocytes to proliferate and secrete IgM, IL-10, and/or IL-6. In vivo studies in nonhuman primates indicate that proinflammatory or humoral immune responses can be selectively facilitated by judicious use of these distinct types of ODN.  相似文献
8.
瑞美隆与氟西汀治疗抑郁症的临床及心理学评价   总被引:9,自引:0,他引:9  
目的 :验证瑞美隆 (米他扎品 )治疗抑郁症的有效性和安全性。方法 :采用DSM -IV(2 96 .2或 2 96 .3)抑郁症的诊断标准 ,共有 34例符合入组 /排除标准。进行为期 6周的瑞美隆每天口服 1次 30mg或氟西汀每天口服 1次 2 0mg的治疗。采用HAMD、CGI评定疗效。采用TESS、体检及实验室检查评价安全性。结果 :经过 6周治疗 ,瑞美隆组和氟西汀组的有效率分别为 88.2 4 %和 82 .35 % ,治愈率分别为 6 4 .71%和 4 1.18% ,两组间有效率和治愈率差异无显著性。瑞美隆和氟西汀组的HAMD量表总分分别由治疗前 34.2 4± 8.79分和 32 .4 7± 5 .4 3分下降至治疗后的 9.6 5± 10 .95分和 9.88± 6 .2 6分 ,两组治疗后各周与治疗前比较差异有显著性 ,两组间差异无显著性。在治疗后第 7、14、2 8天瑞美隆组HAMD量表睡眠紊乱分的减分较氟西汀组明显。瑞美隆组的主要不良反应是眩晕 /头昏、体重增加、疲乏、腹部不适、头痛。氟西汀组的主要不良反应是呕吐 /恶心、体重增加、头痛。结论 :瑞美隆是一种安全、有效的新型抗抑郁药物。具有抗抑郁和抗焦虑作用 ,且有一定改善睡眠作用。  相似文献
9.
采用注塑方法,以医用纳米羟基磷灰石僳酰胺66(n-HA/PA66)复合材料为原料,使用专用发泡剂,制备出了一种具有贯通孔,平均孔隙尺寸约为500衄1的多孔材料,并参照GB/T16886和GB/T16175标准方法,对其生物安全性进行了相关评价。细胞毒性试验、致敏试验、热原试验和溶血试验结果表明本研究制备的多孔n-HA/PA66复合材料无细胞毒性、无致敏性、无热原反应,溶血率为0.59%(〈5%),可初步认为n—HA/PA66多孔材料具有良好的生物安全性,可用于骨组织修复。  相似文献
10.
BACKGROUND: As the main target of sublingual immunotherapy (SLIT) is to reduce at most the occurrence of adverse events (AE), safety represents a critical issue. This aspect deserves particular mention when a higher dose of allergen extract than traditional subcutaneous immunotherapy (SCIT) is required to be effective: that may be up to 500 times that employed for SCIT. OBJECTIVE: All published controlled studies concerning SLIT-swallow were analysed to evaluate AE rates. METHODS: Studies were subdivided in two groups: (i) studies using low allergen dose (LAD), i.e. ranging from 1 to 50 times the dose commonly administered with SCIT, and (ii) studies with high allergen dose (HAD), i.e. ranging from 50 to 500 times the dose administered with SCIT. RESULTS: Twenty-five studies were altogether analysed: 13 studies belonged to the low-dose group, 12 belonged to the high-dose group. We considered all patients with at least one AE. Local reactions were significantly more frequent in the LAD group than in the HAD group (P<0.0001), while there was no difference in the rate of systemic reactions. Severe systemic reactions were never reported. CONCLUSION: This study represents the first analysis of the safety of SLIT concerning the allergen dose employed in the treatment. There is evidence that AE occurrence is substantially not dose-dependent. This fact highlights two main clinical aspects: the elevated tolerability of SLIT in general and the safety of HAD regimen.  相似文献
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号