全文获取类型
收费全文 | 639篇 |
免费 | 85篇 |
国内免费 | 1篇 |
出版年
2023年 | 3篇 |
2022年 | 21篇 |
2021年 | 37篇 |
2020年 | 29篇 |
2019年 | 83篇 |
2018年 | 67篇 |
2017年 | 47篇 |
2016年 | 40篇 |
2015年 | 39篇 |
2014年 | 44篇 |
2013年 | 63篇 |
2012年 | 53篇 |
2011年 | 47篇 |
2010年 | 30篇 |
2009年 | 13篇 |
2008年 | 13篇 |
2007年 | 20篇 |
2006年 | 7篇 |
2005年 | 9篇 |
2004年 | 8篇 |
2003年 | 9篇 |
2002年 | 8篇 |
2001年 | 2篇 |
2000年 | 4篇 |
1999年 | 2篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1978年 | 2篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1972年 | 1篇 |
1966年 | 1篇 |
1933年 | 1篇 |
排序方式: 共有725条查询结果,搜索用时 187 毫秒
51.
52.
Mehdi Rahnavard Mehdi Hassanpour Mahdi Ahmadi Morteza Heidarzadeh Hassan Amini Masoumeh Zirak Javanmard Mohammad Nouri Reza Rahbarghazi Nasser Safaie 《Journal of cellular biochemistry》2019,120(7):11965-11972
Cardiovascular diseases are the main cause of death globally. Many attempts have been done to ameliorate the pathological changes after the occurrence of myocardial infarction. Curcumin is touted as a polyphenol phytocompound with appropriate cardioprotective properties. In this study, the therapeutic effect of curcumin was investigated on acute myocardial infarction in the model of rats. Rats were classified into four groups; control, isoproterenol hydrochloride (ISO) (100 mg/kbw), curcumin (50 mg/kbw), and curcumin plus ISO treatment groups. After 9-day administration of curcumin, levels of lactate dehydrogenase (LDH), creatine kinase (CK), and cardiac troponin I (cTnI) were determined. Superoxide dismutase (SOD) and malondialdehyde (MDA) contents were measured to investigate the oxidative status in infarct rats received curcumin. By using H & E staining, tissue inflammation was performed. Masson’s trichrome staining was conducted to show cardiac remodeling and collagen deposition. The number of apoptotic cells was determined by using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Data showed the serum decrease of LDH, CK, and cTnI in infarct rats after curcumin intake compared to the rats given (ISO) ( P < 0.05). Curcumin was found to reduce oxidative status by reducing SOD and MDA contents ( P < 0.05). Gross and microscopic examinations revealed that the decrease of infarct area, inflammation response and collagen deposition in rats given ISO plus curcumin ( P < 0.05). We noted the superior effect of curcumin to reduce the number of apoptotic cardiomyocytes after 9 days. Data point the cardioprotective effect of curcumin to diminish the complication of infarction by the reduction of cell necrosis and apoptosis in a rat model of experimental infarction. 相似文献
53.
Najmeh Jaberi Atena Soleimani Mehran Pashirzad Hosein Abdeahad Fariba Mohammadi Mahdieh Khoshakhlagh Majid Khazaei Gordon A Ferns Amir Avan Seyed Mahdi Hassanian 《Journal of cellular biochemistry》2019,120(4):4757-4765
Atherosclerosis is an arterial disease associated with inflammation. Thrombin is a procoagulant and proinflammatory serine protease that contributes to the pathology of atherosclerosis by enhancing the expression of cell adhesion molecules, inducing the secretion of proinflammatory cytokines, activating inflammatory responses in atherosclerotic plaques, stimulating proliferation of aortic smooth muscle cells, and exacerbating vascular lesions at sites of injury. Hence, thrombin appears to be an important target for treatment of atherosclerosis and thrombin pharmacological inhibitors have significant therapeutic potency for suppressing inflammatory responses in cardiovascular diseases. This review summarizes the proinflammatory signaling functions of thrombin as well as the therapeutic potency of thrombin inhibitors in the pathogenesis of atherosclerosis and hence their potential therapeutic value in this condition. 相似文献
54.
Matineh Barati Bagherabad Fahimeh Afzaljavan Soodabeh ShahidSales Seyed Mahdi Hassanian Amir Avan 《Journal of cellular biochemistry》2019,120(3):2726-2741
Pancreatic ductal adenocarcinoma (PDAC) is an incidence rate nearly equal to its mortality rate. The poor prognosis of the disease can be explained by the absence of effective biomarkers for screening and early detection, together with the aggressive behavior and resistance to the currently available chemotherapy. The therapeutic failure can also be attributed to the inter-/intratumor genetic heterogeneity and the abundance of tumor stroma that occupies the majority of the tumor mass. Gemcitabine is used in the treatment of PDAC; however, the response rate is less than 12%. A recent phase III trial revealed that the combination of oxaliplatin, irinotecan, fluorouracil, and leucovorin could be an option for the treatment of metastatic PDAC patients with good performance status, although these approaches can result in high toxicity level. Further investigations are required to develop innovative anticancer agents that either improve gemcitabine activity, within novel combinatorial approaches or acts with a better efficacy than gemcitabine. The aim of the current review is to give an overview of preclinical and clinical studies targeting key dysregulated signaling pathways in PDAC. 相似文献
55.
Human cytokeratin 1 (CK1) in human umbilical vein endothelial cells (HUVEC) is expressed on their membranes and is able to bind high molecular weight kininogen (HK) (Hasan, A. A. K., Zisman, T., and Schmaier, A. H. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 3615-3620). New investigations have been performed to demonstrate the HK binding domain on CK1. Four overlapping recombinant (r) CK1 proteins were produced in Escherichia coli by a glutathione S-transferase gene fusion system. Biotin-HK specifically bound to rCK128 and rCK131 in the presence of Zn2+ but not to Deleted1-6rCK131. Recombinant CK128 and rCK131 also inhibited biotin-HK binding to HUVEC with IC50 of 0.4 and 0.5 microM, respectively. Alternatively, rCK114 and Deleted1-6rCK131 did not inhibit binding at concentrations >/=1 microM. Seven sequential 20 amino acid peptides of CK1 were prepared to cover the protein coded by exons 1-3. Only the first peptide (GYG20) coded by exon 1 significantly inhibited HK binding to HUVEC with an IC50 of 35 microM. Fine mapping studies isolated two overlapping peptides also coded by exon 1 (GPV15 and PGG15) that inhibited binding to HUVEC with IC50 of 18 and 9 microM, respectively. A sequence scrambled peptide of PGG15 did not block binding to HUVEC and biotin-GPV20 specifically bound to HK. Peptides GPV15 and PGG15 also blocked prekallikrein activation on endothelial cells. However, inhibition of PK activation by peptide PGG15 occurred at 10-fold lower concentration (IC50 = 1 microM) than inhibition of biotin-HK binding to HUVEC (IC50 = 10 microM). These studies indicate that HK binds to a region of 20 amino acids coded by exon 1 on CK1 which is carboxyl-terminal to its glycine-rich amino-terminal globular domain. Furthermore, HK binding to CK1 modulates PK activation on HUVEC. 相似文献
56.
Suppressor of cytokine signaling 3 regulates proliferation and activation of T-helper cells 总被引:8,自引:0,他引:8
Yu CR Mahdi RM Ebong S Vistica BP Gery I Egwuagu CE 《The Journal of biological chemistry》2003,278(32):29752-29759
57.
Investigations determined the relative preference of prekallikrein (PK) or factor XI/XIa (FXI/FXIa) binding to endothelial cells (HUVECs). In microtiter plates, biotinylated high molecular weight kininogen (biotin-HK) or biotin-FXI binding to HUVEC monolayers or their matrix proteins, but not fibronectin-coated plastic microtiter plate wells, was specifically blocked by antibodies to each of the receptors of HK, uPAR, gC1qR, or cytokeratin 1. Fluorescein isothiocyanate (FITC)-PK specifically bound to HUVEC suspensions without added Zn2+, whereas FITC-FXI or -FXIa binding to HUVEC suspensions required 10 microM added Zn2+ to support specific binding. Plasma concentrations of FXI did not block FITC-PK binding to HUVECs in the absence or presence of 10 microM Zn2+. In the absence of HK, the level of FITC-FXI or -FXIa binding was half that seen in its presence. At physiologic concentrations, PK (450 nM) abolished FITC-FXI or -FXIa binding to HUVEC suspensions in the absence or presence of HK in the presence of 10 microM Zn2+. Released Zn2+ from 2-8 x 10(8) collagen-activated platelets/ml supported biotin-FXI binding to HUVEC monolayers, but platelet activation was not necessary to support biotin-PK binding to HUVECs. At physiologic concentrations, PK also abolished FXI binding to HUVECs in the presence of activated platelets, but FXI did not influence PK binding. PK in the presence or absence of HK preferentially bound to HUVECs over FXI or FXIa. Elevated Zn2+ concentrations are required for FXI but not PK binding, but the presence of physiologic concentrations of PK and HK also prevented FXI binding. PK preferential binding to endothelial cells contributes to their anticoagulant nature. 相似文献
58.
59.
Inference for detecting the existence of an association between a diallelic marker and a trait locus is based on the chi-squared statistic with one degree of freedom. For polymorphic markers with m alleles (2), three approaches are mainly used in practice. First, one may use Pearson's chi-squared statistic with m-1 degrees of freedom (d.f.) but this leads to a loss in test power. Second, one can select an allele to be the most associated and then collapse the other allele categories into a single class. This reduces in a biased way, the locus to a diallelic system. Third, one may use the Terwilliger [J.D. Terwilliger, Am. J. Hum. Genet. 56 (1995) 777] likelihood ratio statistic which has a non-standard unknown limiting probability distribution. In this paper, we propose a new statistic, L(D), based on the second testing approach. We derive the asymptotic probability distribution of L(D) in an easy way. Simulation studies show that L(D) is more powerful than Pearson's chi-squared statistic with m-1 d.f. 相似文献
60.
The circadian periodicity of urinary output, creatinine (Cr) and 5-hydroxyindole acetic acid (5-HIAA) excretion was studied under near-tropical conditions in 130 healthy volunteers (65 men and 65 women, 16-75 years of age) with a diurnal activity from about 06:30 to about 22:00 and nocturnal rest. These volunteers were divided into 4 groups, 16-30, 31-45, 46-60 and 61-75 years of age, comprising 20, 20, 15 and 10 participants of each gender, respectively. A marked circadian rhythm was recorded for urine volume, Cr and 5-HIAA excretion in healthy Indians of different ages. The acrophase tended to be delayed in the older age group. The relative amplitude decreased with advancing age, notably in women. Overall, men produced a larger urine volume as compared to women. Excretions of Cr and 5-HIAA in healthy Indian volunteers of different ages may be influenced by diet, societal relations, climate and/or geographic location. The contribution of such factors in metabolism and degradation warrants further study. 相似文献