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1.
目的 本实验采用免疫组织化学LSAB法,联合检测NM23H1和p53在肝细胞癌原发灶,肝内转移灶和癌旁肝组织中的表达。结果 在癌旁肝组织中,NM23H1表达最高,原发灶较其肝内转移灶表达高。提示NM23H1高表达的肝细胞癌患者术后复发率低,预后较好;p53在癌旁肝组织中无表达,而在原发灶及肝内转移灶中呈显著高表达。提示p53高表达的肝细胞癌患者术后复发率较高,预后较差。在肝原发灶及其肝内转移灶和癌旁肝组织中,NM23H1和p53的表达呈负相关;与患者年龄、性别、肿瘤体积和肝细胞癌组织学类型无相关性,提示NM23H1和p53基因及其蛋白产物在肝细胞癌发生演进过程中起着重要的调控作用。而NM23H1和p53基因及其蛋白产物间相互或协同作用,即p53基因突变或失活后:NM23H1基因随之失活,从而导致NM23H1基因对肝细胞癌癌细胞转移抑制负调控作用的表达,可能是肝细胞癌发生肝内转移的重要分子调控机制之一。 相似文献
2.
乳腺癌 nm23-H_1 蛋白表达的研究 总被引:1,自引:0,他引:1
应用SP免疫组化法检测84例乳腺浸润性导管癌中nm23-H1蛋白的表达,结果显示nm23-H1蛋白在72例(87.5%)有表达。研究表明nm23-H1蛋白的表达水平与淋巴结转移呈负相关(P<0.01),与ER、PR水平呈正相关(P<0.01,P<0.05),而与组织学分级PCNA指数及MDR1-Pgp的表达无关(P>0.05)。 相似文献
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目的进行健康志愿者普卢利沙星片单次和多次口服给药活性代谢物NM394人体药代动力学研究。方法采用三交叉试验设计,12名健康志愿者随机分为3组,普卢利沙星片132.1mg,264.2mg和396.3mg分别单次口服或264.2mg每日2次,连续7日口服。采集肘静脉血,HPLC法测定NM394血浓度,DAS软件计算药动力学参数。结果普卢利沙星片单次口服给药NM394主要药动学参数Cmax为0.64±0.25μg·mL-1,1.06±0.35μg·mL-1和1.45±0.44μg·mL-1,Tmax为0.94±0.22h,1.02±0.17h和0.98±0.23h,t12为8.37±0.70h,7.70±0.82h和7.78±0.77h,AUC0-24为2.93±0.78μg·mL-1·h,4.39±1.05μg·mL-1·h和5.55±1.32μg·mL-1·h,AUC0-∞为3.32±0.84μg·mL-1·h,4.82±1.06μg·mL-1·h和6.10±1.38μg·mL-1·h;连续多次口服给药NM394主要药动学参数Cmax为1.20±0.33μg·mL-1,Tmax为0.67±0.12h,t127.38±1.03h,AUC0-24为5.58±1.25μg·mL-1·h和AUC0-∞为6.09±1.24μg·mL-1·h。结论普卢利沙星片单次口服给药NM394Cmax和AUC呈良好剂量依赖性;单次和多次给药NM394药动学特征无明显差异;多次给药NM394体内无蓄积。 相似文献
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J Abrams 《American heart journal》1984,108(6):1597-1600
8.
《Biomedical and environmental sciences : BES》2022,35(9):782-791
ObjectivePreliminary assessment of rabies virus neutralizing activity, safety and immunogenicity of a recombinant human rabies antibody (NM57) compared with human rabies immunoglobulin (HRIG) in Chinese healthy adults.MethodsSubjects were randomly (1:1:1) allocated to Groups A (20 IU/kg NM57), B (40 IU/kg NM57), or C (20 IU/kg HRIG). One injection was given on the day of enrollment. Blood samples were collected on days –7 to 0 (pre-injection), 3, 7, 14, 28, and 42. Adverse events (AEs) and serious AEs (SAEs) were recorded over a period of 42 days after injection.ResultsAll 60 subjects developed detectable rabies virus neutralizing antibodies (RVNAs) (> 0.05 IU /mL) on days 3, 7, 14, 28, and 42. The RVNA levels peaked on day 3 in all three groups, with a geometric mean concentration (GMC) of 0.2139 IU/mL in Group A, 0.3660 IU/mL in Group B, and 0.1994 IU/mL in Group C. At each follow-up point, the GMC in Group B was significantly higher than that in Groups A and C. The areas under the antibody concentration curve over 0–14 days and 0–42 days in Group B were significantly larger than those in Groups A and C. Fifteen AEs were reported. Except for one grade 2 myalgia in Group C, the other 14 were all grade 1. No SAEs were observed.ConclusionThe rabies virus neutralizing activity of 40 IU/kg NM57 was superior to that of 20 IU/kg NM57 and 20 IU/kg HRIG, and the rabies virus neutralizing activity of 20 IU/kg NM57 and 20 IU/kg HRIG were similar. Safety was comparable between NM57 and HRIG. 相似文献
9.
Ursula G. Sauer Sandra Vogel Alexandra Aumann Annemarie Hess Susanne N. Kolle Lan Ma-Hock Wendel Wohlleben Martina Dammann Volker Strauss Silke Treumann Sibylle Gröters Karin Wiench Bennard van Ravenzwaay Robert Landsiedel 《Toxicology and applied pharmacology》2014
The applicability of rat precision-cut lung slices (PCLuS) in detecting nanomaterial (NM) toxicity to the respiratory tract was investigated evaluating sixteen OECD reference NMs (TiO2, ZnO, CeO2, SiO2, Ag, multi-walled carbon nanotubes (MWCNTs)). Upon 24-hour test substance exposure, the PCLuS system was able to detect early events of NM toxicity: total protein, reduction in mitochondrial activity, caspase-3/-7 activation, glutathione depletion/increase, cytokine induction, and histopathological evaluation. Ion shedding NMS (ZnO and Ag) induced severe tissue destruction detected by the loss of total protein. Two anatase TiO2 NMs, CeO2 NMs, and two MWCNT caused significant (determined by trend analysis) cytotoxicity in the WST-1 assay. At non-cytotoxic concentrations, different TiO2 NMs and one MWCNT increased GSH levels, presumably a defense response to reactive oxygen species, and these substances further induced a variety of cytokines. One of the SiO2 NMs increased caspase-3/-7 activities at non-cytotoxic levels, and one rutile TiO2 only induced cytokines. Investigating these effects is, however, not sufficient to predict apical effects found in vivo. Reproducibility of test substance measurements was not fully satisfactory, especially in the GSH and cytokine assays. Effects were frequently observed in negative controls pointing to tissue slice vulnerability even though prepared and handled with utmost care. Comparisons of the effects observed in the PCLuS to in vivo effects reveal some concordances for the metal oxide NMs, but less so for the MWCNT. The highest effective dosages, however, exceeded those reported for rat short-term inhalation studies. To become applicable for NM testing, the PCLuS system requires test protocol optimization. 相似文献
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《Regulatory toxicology and pharmacology : RTP》2014,68(3):392-408
Neutral Methacrylate Copolymer is a fully polymerised copolymer used in the pharmaceutical industry to permit pH-independent delayed release of active ingredients from oral dosage forms. This function has potential use with food supplements and this article describes available information on the safety of the substance.Oral administration of radiolabelled copolymer to rats resulted in the detection of chemically unchanged copolymer in the faeces, with negligible absorption. Safety studies revealed no adverse toxicity following repeated administration at doses of up to 2000 mg/kg bw/d in a sub-chronic study in rats or 250 mg/kg bw/d in a sub-chronic study in dogs. No reproductive toxicity occurred at up to 2000 mg/kg bw/d in rats or rabbits. The substance shows no evidence of genotoxicity, has low acute toxicity and no irritation or sensitisation potential.An ADI value of 20 mg/kg bw was concluded from two alternative approaches. Daily exposure from use in dietary supplements is estimated as up to 10.0 mg/kg bw in adults and 13.3 mg/kg bw in children. There would therefore appear to be no safety concerns under the intended conditions of use. The information provided is intended to support an evaluation that the substance may be “generally recognized as safe” (GRAS). 相似文献