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41.
Biermer M Schlosser B Fülöp B van Bömmel F Brodzinski A Heyne R Keller K Sarrazin C Berg T 《Journal of viral hepatitis》2012,19(8):547-553
Incomplete suppression of hepatitis C virus (HCV) replication with persistence of minimal viremia (partial virologic response) leading to treatment failure can be observed in a significant proportion of HCV type 1-infected patients during antiviral therapy. Recently, high-dose intravenous silibinin has demonstrated strong antiviral activity against HCV. We were therefore interested in whether patients with partial virologic response can be rescued by the on-treatment addition of a short-term course of high-dose intravenous silibinin infusions. Twenty patients who failed to achieve a complete virologic response to different interferon-based regimens qualified for the rescue strategy and received 1400 mg/day silibinin infusions on two consecutive days. Complete viral suppression (below the limit of detection <6 IU/mL, TMA assay) could be induced in 13 of 20 patients within the first week after the short-term silibinin infusion, and all but one of them also remained HCV RNA negative during the subsequent follow-up period on continued peginterferon plus ribavirin treatment. In the remaining seven patients, no complete suppression could be achieved although four showed a significant HCV RNA reduction in response to silibinin. Silibinin infusions were generally well tolerated, and activation of abdominal peristalsis with nausea, diarrhoea and vomiting were the most prominent side effects. Of the twelve patients who exhibited a durable response to peginterferon and ribavirin treatment, three achieved an SVR, two achieved a week 12 SVR and four suffered a viral relapse. Three patients could not complete the assigned antiviral treatment with peginterferon alpha and ribavirin for nonvirological reasons. Short-term administration of high-dose intravenous silibinin might be an interesting approach to rescue patients with ongoing minimal residual viremia while on interferon-based therapy. These preliminary findings may stimulate further studies to evaluate more refined therapeutic strategies. 相似文献
42.
目的:应用拉米夫定联合水飞蓟宾治疗 E 抗原阳性的慢性乙型肝炎,通过治疗前后的相关血液指标变化判断疗效,为个体化治疗提供依据。方法选取 E 抗原阳性慢性乙型肝炎患者226例,按肝功能损伤程度分为轻度组55例、中度组94例和重度组77例,均给予口服拉米夫定100 mg,每日1次及服用水飞蓟宾70 mg,每日3次,疗程6个月。分别对治疗前后的相关血液指标进行分析。结果治疗6个月后,轻度组及中度组患者血清 ALT 复常率、E 抗原阴转率及 HBV-DNA 阴转率有不同程度的改善,而重度组上述指标则均显著提高(P <0.05)。结论拉米夫定联合水飞蓟宾治疗更能有效抑制 HBV-DNA 的复制,明显促进血清 ALT 复常率及提高 E 抗原阴转率,尤其是肝功能损伤程度重者;在一定程度上提高治疗慢性乙型肝炎的疗效。 相似文献
43.
Silibinin and its 2,3‐dehydro‐derivative inhibit basal cell carcinoma growth via suppression of mitogenic signaling and transcription factors activation 下载免费PDF全文
44.
目的 研究水飞蓟宾(SIL)对局灶性脑缺血再灌注损伤大鼠的保护作用,并探讨其可能的作用机制。方法 取112只清洁级雄性大鼠随机分为6组:假手术组、模型对照组、水飞蓟宾(100、200和400 mg·kg-1)预处理组和尼莫地平(32 mg·kg-1)预处理组,通过中动脉线栓法制备局灶性脑缺血再灌注大鼠模型。再灌注6 h后,进行神经功能评分,分析测定脑组织梗死体积及含水量;通过苏木精-尹红(HE)染色法观察脑组织形态学变化;测定血清中磷酸肌酸激酶(CPK)、乳酸脱氢酶(LDH)含量及总抗氧化能力(T-AOC)水平;测定脑组织中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性和丙二醛(MDA)含量;通过TUNEL染色观察神经细胞凋亡状况并计算凋亡指数(AI),通过Western blot方法测定脑组织中NF-κB蛋白表达并进行半定量分析。结果 与模型组相比,水飞蓟宾(200和400 mg·kg-1)预处理组大鼠神经功能评分显著降低、脑梗死体积和含水量均显著降低,脑组织病理形态学变化及神经细胞凋亡均明显减轻,凋亡指数显著降低;脑组织中SOD、CAT活性显著升高且MDA含量显著降低;血清中CPK,LDH含量显著降低;脑组织中NF-κB蛋白表达量显著降低;水分蓟宾400 mg·kg-1预处理组血清中T-AOC水平显著升高;差异均具有统计学意义(P<0.05,P<0.01)。结论 水分蓟宾对局灶性脑缺血再灌注损伤大鼠具有保护作用,其作用机制可能与水分蓟宾能够改善局灶性脑缺血再灌注损伤大鼠脑组织中抗氧化酶活性、抑制氧化应激损伤有关。 相似文献
45.
Anticancer Potential of Silibinin Loaded Polymeric Nanoparticles against Breast Cancer Cells: Insight into the Apoptotic Genes Targets 下载免费PDF全文
Ali PourgholiMehdi Dadashpour Akram MousapourAkram Firouzi AmandiNosratollah Zarghami 《Asian Pacific journal of cancer prevention》2021,22(8):2587-2596
Silibinin (SIL) is a natural polyphenolic flavonoid with multiple biological and anti-cancer features. However, the complex hydrophobic nature and inadequate bioavailability of SIL hinder its efficiency at tumor sites. Investigating the possibility of an extensive strategy for better treatment of breast cancer, we carried out a comparative exploration of the inhibitory effect of SIL and SIL loaded PLGA-PEG nanoparticle (SIL-NPs) on the expression of the proapoptotic target genes, which is considered as an influential molecular target for treatment of breast cancer. The main diameter of SIL-NPs was 220 ± 6.37 and 150 ± 23.14 nm via DLS and FE-SEM respectively. Furthermore, the zeta potential of PLGA-PEG and SIL-NPs was -5.48±0.13 and -6.8±0.26 mV respectively. SIL encapsulation efficiency and drug release were determined by about 82.32 % by analyzing the calibration curve of SIL absorbance at 570 nm. Cytotoxicity of SIL and SIL-NPs was conducted by MTT assay after 24, 48, and 72 h of exposure times, and the gene expression levels of apoptotic genes, p53 and hTERT was measured by real-time PCR. Evaluation of drug toxicity revealed that SIL-NPs represents higher cytotoxic effects than pure SIL in a time and dose-dependent manner. Moreover, the results demonstrated that SIL-NPs could induce apoptosis in breast cancer cells by upregulation of caspase-3, caspase-7, p53 and Bax, along with Bcl-2, hTERT, survivin and Cyclin D1 down regulation. Our results indicated that PLGA-PEG can be used as stable carriers in nano-dimensions and SIL-NPs can be considered as a promising pharmacological agent for cancer therapy. 相似文献
46.
水飞蓟宾对急性肝损伤中肝细胞胀亡的影响及其机制 总被引:7,自引:2,他引:7
目的:探讨水飞蓟宾(SIL)在急性肝损伤中对肝细胞胀亡的影响及其机制.方法:用D-氨基半乳糖(D-GalN)诱导大鼠急性肝损伤模型,用SIL进行干预,于不同时间点检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)活性及肝组织核转录因子-κB(NF-κB)活性,观察肝组织病理及肝细胞胀亡情况,并计算胀亡指数(OI).结果:SIL能明显降低急性肝损伤模型大鼠血清ALT、AST活性(P均<0.05),抑制NF-κB活性(P<0.05),镜下显示肝组织损伤减轻程度,减少肝细胞胀亡,降低OI(P均<0.05).结论:SIL可减少D-GalN所致大鼠肝细胞胀亡,其机制可能与抑制NF-κB活性有关. 相似文献
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50.
Silibinin and colorectal cancer chemoprevention: a comprehensive
review on mechanisms and efficacy 下载免费PDF全文
Globally, the risk of colorectal cancer (CRC) as well as the incidence of mortality associated with CRC is increasing.
Thus, it is imperative that we look at alternative approaches involving intake of non-toxic natural dietary/non-dietary
agents, for the prevention of CRC. The ultimate goal of this approach is to reduce the incidence of pre-neoplastic
adenomatous polyps and prevent their progression to more advanced forms of CRC, and use these natural agents as a
safe intervention strategy during the clinical course of this deadly malignancy. Over the years, pre-clinical studies have
shown that silibinin (a flavonolignan isolated from the seeds of milk thistle, Silybum marianum) has strong preventive
and therapeutic efficacy against various epithelial cancers, including CRC. The focus of the present review is to provide
a comprehensive tabular summary, categorically for an easy accessibility and referencing, pertaining to the efficacy and
associated mechanisms of silibinin against CRC growth and progression. 相似文献