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31.
Pui Y. Lee-Law Paula Olaizola Francisco J. Caballero-Camino Laura Izquierdo-Sanchez Pedro M. Rodrigues Alvaro Santos-Laso Mikel Azkargorta Felix Elortza Maria L. Martinez-Chantar Maria J. Perugorria Patricia Aspichueta Marco Marzioni Nicholas F. LaRusso Luis Bujanda Joost P.H. Drenth Jesus M. Banales 《Journal of hepatology》2021,74(2):394-406
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32.
S-腺苷蛋氨酸对人胃癌细胞系SGC-7901和BGC-823的影响 总被引:1,自引:0,他引:1
目的 观察S-腺苷蛋氨酸(SAM)对体外培养的人胃癌细胞系SGC-7901和BGC-823细胞增殖、细胞周期、凋亡和侵袭力的影响,及对这两种细胞中c-myc 和尿激酶型纤溶酶原激活剂(uPA)基因甲基化状态及表达的影响.方法 采用四甲基偶氮唑盐法检测SAM对SGC-7901和BGC-823细胞增殖的影响.应用不同浓度(0、2、4 mmol/L)的SAM处理SGC-7901和BGC-823细胞72 h后,用流式细胞仪检测各组细胞周期和凋亡;Transwell法检测各组细胞侵袭力;分别使用逆转录聚合酶链反应(RT-PCR)、蛋白质印迹法和甲基化特异性PCR(MSP)方法检测各组细胞中c-myc和uPA基因mRNA和蛋白的表达及甲基化状态.结果 0.5~32 mmol/L SAM处理SGC-7901和BGC-823细胞24、48、72 h后,随SAM浓度增大和作用时间延长,细胞增殖受到明显抑制(均P<0.05),生长抑制率也逐渐增大,72 h IC50分别为SGC-7901 5.40 mmol/L、BGC-823 4.01 mmol/L.经过不同浓度(0、2、4 mmol/L)SAM处理SGC-7901和BGC-823细胞72 h后,随SAM浓度增加,G0/G1期细胞比例均逐渐增加,且差异有统计学意义(分别P<0.05和P<0.01),细胞增殖指数明显低(分别P<0.05和P<0.01);与对照组凋亡率(0.33±0.09)比较,SGC-7901 2 mmol/L组(5.79±0.75)和4 mmol/L组(10.19±0.60)均高(均P<0.01);与对照组凋亡率(0.95±0.19)比较,BGC-823 2 mmol/L组(6.23±0.75)和4 mmol/L组(11.82±1.14)均高(均P<0.01).细胞侵袭力均受到明显抑制,差异均有统计学意义(均P<0.01),SGC-7901 2、4 mmol/L组侵袭抑制率分别是51.07%和80.69%,BGC-823 2、4 mmol/L组侵袭抑制率分别是48.57%和84.10%.除了BGC-823细胞的2 mmol/L组c-myc 基因,其余各组细胞c-myc 基因和uPA基因的mRNA表达均明显减弱(分别P<0.05和P<0.01);c-myc基因和uPA基因均恢复甲基化状态.结论 SAM可促进SGC-7901和BGC-823胃癌细胞凋亡,抑制增殖,使细胞在G0/G1期受阻;使细胞侵袭力受到抑制;能够逆转胃癌细胞c-myc基因和uPA基因的低甲基化状态,调控c-myc基因和uPA基因的表达. 相似文献
33.
Ranwa Alsayed Faizeh AL Quobaili Samir Srour Jürgen Geisel Rima Obeid 《Metabolism: clinical and experimental》2013
Objective
Congenital Heart Defects (CHD) may be related to nutritional deficiencies affecting the methylation cycle. We aimed to study the metabolic markers of the betaine homocysteine methyl transferase (BHMT) pathway in children with CHD and their mothers compared to children without CHD and their mothers.Materials and Methods
Children with CHD (n = 105, age < 3 years) and mothers of 80 of the affected children were studied. The controls were non-CHDs children of comparable age as the CHD group (n = 52) and their mothers (n = 50). We measured serum or plasma concentrations of the metabolites of the methylation cycle homocysteine (HCY), methylmalonic acid (MMA), cystathionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), betaine, choline, and dimethylglycine (DMG).Results
Children with CHD had higher plasma SAM (131 vs. 100 nmol/L) and DMG (8.7 vs. 6.0 μmol/L) and lower betaine/DMG ratio (7.5 vs. 10.2) compared to the controls. Mothers of CHD children showed also higher DMG (6.1 vs. 4.1 µmol/L) and lower betaine/DMG ratio compared with the mothers of the controls. Higher SAM levels were related to higher cystathionine, MMA, betaine, choline, and DMG. MMA elevation in the patients was related to higher HCY, SAM, betaine and DMG.Conclusions
Elevated DMG in CHD children and their mothers compared to the controls can indicate upregulation of the BHMT pathway in this disease group. Nutritional factors are related to metabolic imbalance during pregnancy that may be related to worse birth outcome. 相似文献34.
35.
Martínez-Chantar ML Vázquez-Chantada M Garnacho M Latasa MU Varela-Rey M Dotor J Santamaria M Martínez-Cruz LA Parada LA Lu SC Mato JM 《Gastroenterology》2006,131(1):223-232
BACKGROUND & AIMS: After liver injury, hepatic S-adenosylmethionine (SAM) content decreases, and the blockage this molecule imposes on hepatocyte proliferation is released, facilitating liver regeneration. This activity of SAM is important for normal liver function because mice deficient in hepatic SAM display abnormal liver regeneration and develop hepatocellular carcinoma. How SAM regulates hepatocyte growth is unclear, but because SAM blocks hepatocyte growth factor (HGF)-induced cyclin D1 expression and DNA synthesis without affecting HGF-induced extracellular signal-regulated kinase phosphorylation, the mitogen-activated protein kinase (MAPK) pathway is probably not the target. METHODS: The effects of SAM on AMPK, HuR localization were assessed in rat hepatocytes after HGF, AICAR, and SAM treatment. RESULTS: We show here that HGF and 5-aminoimidazole-4-carboxamide-riboside (AICAR), an activator of AMP-activated protein kinase (AMPK), induce the phosphorylation of AMPK in hepatocytes and that SAM blocks this process. We also show that HGF- and AICAR-induced AMPK activation stimulate the transport from nucleus to cytoplasm of HuR, an RNA-binding protein that increases the half-life of target mRNA such as cyclin A2, and that SAM blocks this process. We found that, in hepatocytes, AICAR increases HuR binding to cyclin A2 messenger RNA (mRNA) as well as the expression and stability of this mRNA and that SAM blocks these events. Consistently, we found that AICAR induces hepatocyte proliferation and that SAM blocks this effect. Finally, we found that liver AMPK phosphorylation, cytoplasmic HuR, and binding of HuR to HuR-target mRNA and the steady-state levels of these mRNA are increased in knockout mice deficient in hepatic SAM. CONCLUSIONS: Our results yield novel insights about the mechanism by which SAM inhibits cell-cycle progression in the liver. 相似文献
36.
Intermediates in the folate-dependent methylation pathways may play a role in the etiology and treatment of such mental disorders as major depression. These pathways include a step dependent on a riboflavin (B2)-derived coenzyme, flavin adenine dinucleotide (FAD), which is reportedly sensitive to thyroid status and to phenothiazine and tricyclic drug exposure. In a sample of 52 male and female acute psychiatric inpatients, 17% (n = 9) showed B2 deficiency (i.e., insufficient FAD activity) on a functional red blood cell enzyme assay, but only one B2-deficient individual showed deficiency in another B-complex vitamin (folate). All patients with B2 deficiency were women, who were also significantly younger than the rest of the sample. The B2-deficient women had significantly lower thyroxine levels, even when controlling for sex and covarying for age. B2-deficient patients exhibited a nonsignificant trend toward more unipolar depression (44% vs 14%), but not toward bipolar or schizophrenic disorders. As in a previous study, drug exposure did not show a relationship to riboflavin deficiency in this sample. The findings suggest that B2 (FAD) activity may serve as a sensitive marker of thyroxine status in certain female psychiatric inpatients and that B2 deficiency may play an etiological role in defects of the methylation pathways in a subset of mentally ill individuals. 相似文献
37.
目的 分析S- 腺苷蛋氨酸联合利胆药对妊娠期肝内胆汁淤积症产妇胎盘组织中NF-κB 相关
因子表达水平及Th17/Treg 平衡的影响。方法 选取2012 年12 月-2016 年12 月于南通大学附属医院妇收
治的96 例妊娠期肝内胆汁淤积症产妇,并按随机数字表法分为对照组和观察组。对照组采用利胆药进行治疗;
观察组采用S- 腺苷蛋氨酸联合利胆药治疗。对比两组患者瘙痒症状评分、TNF-α、HIF-1α、TGF-β1、
总胆汁酸(TBA)及IL-17 的含量,并分析患者Th17、Treg 细胞相对数及Th17/Treg 的变化情况。结果 两
组患者血清中TNF-α、HIF-1α、TGF-β1、TBA 及IL-17 比较有差异(P <0.05)。两组患者瘙痒症状评
分、Th17、Treg 细胞相对数及Th17/Treg 比率比较有差异(P <0.05)。两组患者治疗的总有效率比较有差
异(P <0.05)。两组患者早产率、胎儿宫内窘迫率及新生儿窒息率比较有差异(P <0.05)。结论 采用S- 腺
苷蛋氨酸联合利胆药治疗妊娠期肝内胆汁淤积症产妇,能有效改善患者NF-κB 相关因子表达水平及Th17/
Treg 平衡,缓解患者的瘙痒症状,减少新生儿不良反应的发生。 相似文献
38.
39.
Intrahepatic cholestasis of pregnancy poses a great risk to both maternal and fetal health. Despite extensive research, much of the pathogenesis of this disorder is unknown. The increase in bile acids observed in patients with intrahepatic cholestasis of pregnancy has been noted to cause a change in the immune system from the normally mediated TH2 response to one that is more oriented towards TH1. In this literature review, we have critically reviewed the current literature regarding the changes in the immune system and the potential effects of immunological changes in the management of the patient. The current treatment, ursodeoxycholic acid, is also discussed along with potential combination therapies and future directions for research. 相似文献
40.