全文获取类型
收费全文 | 228篇 |
免费 | 20篇 |
国内免费 | 13篇 |
专业分类
基础医学 | 33篇 |
临床医学 | 2篇 |
内科学 | 103篇 |
神经病学 | 6篇 |
特种医学 | 12篇 |
综合类 | 45篇 |
预防医学 | 6篇 |
药学 | 33篇 |
中国医学 | 20篇 |
肿瘤学 | 1篇 |
出版年
2022年 | 1篇 |
2021年 | 2篇 |
2020年 | 9篇 |
2019年 | 3篇 |
2018年 | 2篇 |
2017年 | 5篇 |
2016年 | 7篇 |
2015年 | 6篇 |
2014年 | 8篇 |
2013年 | 14篇 |
2012年 | 5篇 |
2011年 | 8篇 |
2010年 | 4篇 |
2009年 | 4篇 |
2008年 | 13篇 |
2007年 | 7篇 |
2006年 | 8篇 |
2005年 | 5篇 |
2004年 | 9篇 |
2003年 | 13篇 |
2002年 | 8篇 |
2001年 | 10篇 |
2000年 | 10篇 |
1999年 | 9篇 |
1998年 | 7篇 |
1997年 | 8篇 |
1996年 | 8篇 |
1995年 | 9篇 |
1994年 | 4篇 |
1993年 | 5篇 |
1992年 | 5篇 |
1991年 | 2篇 |
1990年 | 7篇 |
1989年 | 6篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 9篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 4篇 |
1979年 | 1篇 |
排序方式: 共有261条查询结果,搜索用时 15 毫秒
51.
Cerebral malaria is associated with the circulating levels of tumour necrosis factor alpha (TNF‐α) and transforming growth factor β (TGF‐β), but association between these two cytokines and implications in splenocyte apoptosis remain largely obscured. We have evaluated the outcome of TGF‐β and TNF‐α production in the context of splenocyte apoptosis during Plasmodium berghei ANKA (PbA) infection. Blood‐stage PbA infection confirmed blood–brain barrier disruption, disarray of white pulp, increase in percentage of sub‐G0/G1 and splenocyte apoptosis. Flow cytometric analysis reveals up‐regulation of Fas‐L followed by caspase‐8 and caspase‐3 activation and signifies possible involvement of Fas‐L‐mediated splenocyte apoptosis. We have observed down‐regulation of TGF‐β and up‐regulation of TNF‐α in tissue and serum level, respectively, during PbA infection. Association between the production of TGF‐β and the severity of malaria infection in splenocytes was verified with TGF‐β inhibitor that exacerbated the apoptotic process. In contrary, TNF‐α inhibitor causes significant delay in apoptotic process, but could not alter the lethality of parasite. Thus, results from this study suggest that the critical balance between TGF‐β and TNF‐α might have a key role on Fas‐L‐mediated splenocyte apoptosis during experimental cerebral malaria. 相似文献
52.
Richard K. Cimanga Gaston L. Tona Gauthier K. Mesia Oscar K. Kambu Donatien P. Bakana Pascal D.T. Kalenda 《Pharmaceutical biology》2013,51(9):677-681
AbstractThe EtOH, CH2Cl2, and petroleum ether extracts from Morinda lucida. Benth. leaves have been shown to exhibit an in vitro. antiplasmodial activity against a chloroquine-sensitive Plasmodium falciparum. strain with IC50 values 5.7 ± 1.3, 5.2 ± 0.8, and 3.9 ± 0.3 µg/mL, respectively. In vivo., at a daily oral dose of 200 mg/kg body weight, they produced at least 62.5%, 67.5%, and 72.2% reduction of parasitemia in mice infected with Plasmodium berghei berghei., respectively. A bioassay-guided fraction of the most active petroleum ether extract resulted in the isolation of two known triterpenic acids as ursolic acid 1 and oleanolic acid 2. In vitro., 1 and 2 exhibited an antiplasmodial activity with IC50 values of 3.1 ± 1.3 and 15.2 ± 3.4 µg/mL, respectively. In vivo., at a daily dose of 200 mg/kg body weight, they produced 97.7% and 37.4% chemosuppression, respectively. However, all tested samples were inactive in vitro. against chloroquine-resistant Plasmodium falciparum. (K1) at the highest tested concentration of 25 µg/mL. 相似文献
53.
目的探讨疟疾感染早期根治性治疗对再感染过程中树突状细胞(dendritic cells,DCs)成熟和功能的影响。方法用伯氏疟原虫(Plasmodium bergheiANKA,PbA)感染DBA/2小鼠,感染后3d进行根治性治疗,并于初次感染后90d进行再感染。通过吉姆萨薄血膜染色法计数红细胞感染率,流式细胞术检测再感染前(0d)和再感染后(1d、3d、5d)不同时间点脾细胞中表达CD80、CD86、CD40和MHC-II分子的DCs以及活化性T细胞的百分含量。结果同种疟原虫再感染后,根治性治疗小鼠仅出现短暂的低水平虫体血症;表达CD80、CD86、CD40和MHC-II分子的DCs百分率均于再感染后第3d出现了有意义的升高;再感染后第1-5d活化性T细胞百分率持续升高。结论初次感染早期根治性治疗后,同种疟原虫再攻击可诱导DCs的成熟和功能的发挥。 相似文献
54.
用伯氏鼠疟模型筛选了17个2,4-二氨基-6-取代氨基磺酰喹唑啉类化合物。初步结果显示,化合物Ⅰ4,Ⅰ5,Ⅰ10,Ⅰ11和Ⅰ12口服有较好抗疟作用,对正常敏感株(N)的SD50为0.43~2.4mg/kg×4d,高度抗氯喹株(RC)为0.19~0.42mg/kg×4d,(NK65)株为7.2~100mg/kg×4d,抗磺胺株(ORA)为11~76 mg/kg×4d。上述结果表明,该类化合物对(RC)株的疗效显著优于(N)株,但对(NK65)株的疗效较差,与磺胺类药物有轻度交叉抗性。 相似文献
55.
56.
目的 探讨感染伯氏疟原虫的C57BL/6小鼠脾脏不同免疫细胞的含量及表面分子变化。方法 将C57BL/6小鼠尾静脉注射伯氏疟原虫进行感染,6 d后分离感染组和正常对照组小鼠的脾脏,制备单细胞悬液,然后通过流式细胞术检测小鼠CD8+T细胞、γδT细胞和T细胞的含量及其表面分子CXCR3、CD69、CD62L的表达水平变化情况。结果 感染伯氏疟原虫的小鼠脾脏CD8+T细胞(5.51%±0.76%)、γδT细胞(0.31%±0.03%)和T细胞(18.60%±3.37%)的百分比含量较正常组(14.04%±1.31%、0.75%±0.07%、33.27%±3.76%)明显减低,差异有统计学意义(P<0.01);与正常组(21.45%±0.10%、33.49%±3.17%、16.72%±2.16%)相比,感染组小鼠脾脏CD8+T细胞、γδT细胞和T细胞的CXCR3(6.30%±0.15%、18.34%±0.61%、5.25%±0.25%)均明显下调(P<0.05);感染组小鼠脾脏CD8+T细胞、γδT细胞和T细胞的CD62L(67.98%±1.18%、54.37%±0.98%、55.06%±1.53%)较正常组(91.96%±0.75%、71.38%±1.02%、82.10%±1.04)%)均明显下调(P<0.05),而感染组小鼠脾脏CD8+T细胞、γδT细胞和T细胞的CD69 (28.13%±0.37%、42.58%±2.06%、34.65%±0.43%)表达水平比正常组(3.70%±0.62%、11.59%±0.41%、7.69%±1.56%)高,差异有统计学意义(P<0.01)。结论 感染伯氏疟原虫的C57BL/6小鼠脾脏CD8+T细胞、γδT细胞和T细胞及其表达的CXCR3和CD62L均明显下调,而CD69的表达水平升高,提示机体感染疟原虫后,小鼠的T淋巴系细胞增殖不明显,但其迁移情况有所不同,存在一定的复杂性。 相似文献
57.
58.
Emmanuel T Idowu Henry CN Ajaegbu Ahmed I Omotayo Oluwagbemiga O Aina Olubunmi A Otubanjo 《African health sciences》2015,15(4):1262-1270
Background
Lime extracts of powdered combination of seeds of Picralima nitida, stem bark of Alstonia boonei and leaves of Gongronema latifolium is a common remedy used in the treatment of malaria in South Western Nigeria.Objective
To determine the antiplasmodial activities of the combined herbal extracts and its impact on the haematological, hepatological and renological parameters in mice.Methods
The 4-day suppressive and curative tests were used to assess the antiplasmodial activities of the extract in mice infected with chloroquine-sensitive Plasmodium berghei at concentration of 200mg/kg, 400mg/kg and 800mg/kg body weight. The haematological parameters including red blood cells, white blood cells, packed cell volume and haemoglobin count were analysed with an auto analyser. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were determined, while urea, protein and creatinine were analysed by standard procedural methods.Results
The 4-day suppressive test revealed that the test extract achieved percentage suppression of 39.0%, 41.6% and 54.68% for the 200mg/kg, 400mg/kg and 800mg/kg concentration respectively. Additionally, the curative test achieved a high percentage suppression of 80.97%, 83.84% and 86.16% at the 200mg/kg, 400mg/kg and 800mg/kg concentration respectively. The extracts did not induce significant change on haematological parameters (P>0.05), while significant elevation in the values of the ALT and AST (P<0.05) was observed and elevation of creatinine (P<0.05) at 800mg/kg.Conclusions
The results support the traditional use of the herbal combination in the treatment of malaria, however the liver cells were impacted by the extracts in bioassay conducted with mice. 相似文献59.
Jennifer Palomo Flora Reverchon Julie Piotet Anne‐Gaelle Besnard Aurélie Couturier‐Maillard Isabelle Maillet Maurel Tefit François Erard Dominique Mazier Bernhard Ryffel Valérie F. J. Quesniaux 《European journal of immunology》2015,45(5):1354-1365
Cerebral malaria, a severe complication of Plasmodium falciparum infection, can be modeled in murine Plasmodium berghei ANKA (PbA) infection. PbA‐induced experimental cerebral malaria (ECM) is CD8+ T‐cell mediated, and influenced by TH1/TH2 balance. Here, we show that IL‐33 expression is increased in brain undergoing ECM and we address the role of the IL‐33/ST2 pathway in ECM development. ST2‐deficient mice were resistant to PbA‐induced neuropathology. They survived >20 days with no ECM neurological sign and a preserved cerebral microcirculation, while WT mice succumbed within 10 days with ECM, brain vascular leakage, distinct microvascular pathology obstruction, and hemorrhages. Parasitemia and brain parasite load were similar in ST2‐deficient and WT mice. Protection was accompanied by reduced brain sequestration of activated CD4+ T cells and perforin+ CD8+ T cells. While IFN‐γ and T‐cell‐attracting chemokines CXCL9 and CXCL10 were not affected in the absence of functional ST2 pathway, the local expression of ICAM‐1, CXCR3, and LT‐α, crucial for ECM development, was strongly reduced, and this may explain the diminished pathogenic T‐cell recruitment and resistance to ECM. Therefore, IL‐33 is induced in PbA sporozoite infection, and the pathogenic T‐cell responses with local microvascular pathology are dependent on IL‐33/ST2 signaling, identifying IL‐33 as a new actor in ECM development. 相似文献
60.
Apigenin inhibits growth of the Plasmodium berghei and disrupts some metabolic pathways in mice 下载免费PDF全文
Mahdi Amiri Abbasali Nourian Maryam Khoshkam Ali Ramazani 《Phytotherapy research : PTR》2018,32(9):1795-1802
Due to the challenges in the control, prevention, and eradication of parasitic diseases like malaria, there is an urgent need to discover new therapeutic agents. Plant‐derived medicines may open new ways in the field of antiplasmodial therapy. This study is aimed to investigate the toxicity and in vivo antiplasmodial activity of apigenin, a dietary flavonoid. Apigenin cytotoxicity was investigated on Huh7 cell line, brine shrimp (Artemia salina) larva, and human red blood cells. In vivo toxicity of apigenin was assessed by metabolomics approaches. Apigenin exhibited significant suppression of parasitemia in a dose‐dependent manner; it suppressed Plasmodium berghei growth by 69.74%, 50.3%, and 49.23% at concentrations of 70, 35, and 15 mg/kg/day, respectively. The IC50 value for apigenin after 24 hr exposure to Huh7 cells was 225 μg/ml. Apigenin did not show noticeable toxicity on A. salina and also on the membrane integrity of red blood cells. After 24 hr exposure of mice to apigenin, alterations were seen in the metabolism of glucocorticoids and mineralocorticoids, bile acid metabolism (alternative pathway), sulfur metabolism, bile acid metabolism, metabolism of estrogens and androgens, cholesterol catabolism, and biosynthesis of cholesterol. These findings indicate that apigenin has potential in vivo antiplasmodial activity against P. berghei infected mice with high selectivity against malaria, but it can disrupt some metabolic pathways in mice. 相似文献