全文获取类型
收费全文 | 1000篇 |
免费 | 77篇 |
出版年
2023年 | 9篇 |
2022年 | 10篇 |
2021年 | 20篇 |
2020年 | 17篇 |
2019年 | 15篇 |
2018年 | 31篇 |
2017年 | 15篇 |
2016年 | 29篇 |
2015年 | 52篇 |
2014年 | 60篇 |
2013年 | 94篇 |
2012年 | 76篇 |
2011年 | 67篇 |
2010年 | 47篇 |
2009年 | 19篇 |
2008年 | 33篇 |
2007年 | 48篇 |
2006年 | 35篇 |
2005年 | 36篇 |
2004年 | 43篇 |
2003年 | 30篇 |
2002年 | 36篇 |
2001年 | 18篇 |
2000年 | 16篇 |
1999年 | 13篇 |
1998年 | 13篇 |
1997年 | 4篇 |
1996年 | 5篇 |
1995年 | 4篇 |
1994年 | 5篇 |
1993年 | 7篇 |
1992年 | 11篇 |
1991年 | 16篇 |
1990年 | 7篇 |
1989年 | 7篇 |
1988年 | 9篇 |
1987年 | 8篇 |
1986年 | 12篇 |
1985年 | 13篇 |
1984年 | 10篇 |
1983年 | 5篇 |
1979年 | 7篇 |
1976年 | 7篇 |
1975年 | 6篇 |
1974年 | 5篇 |
1973年 | 4篇 |
1970年 | 4篇 |
1968年 | 6篇 |
1967年 | 5篇 |
1966年 | 4篇 |
排序方式: 共有1077条查询结果,搜索用时 0 毫秒
31.
32.
Hona Hosseinpoor Aida Iraji Najmeh Edraki Somayeh Pirhadi Mahshid Attarroshan Mahsima Khoshneviszadeh Mehdi Khoshneviszadeh 《化学与生物多样性》2020,17(8)
Tyrosinase is a type 3 copper enzyme responsible for skin pigmentation disorders, skin cancer, and enzymatic browning of vegetables and fruits. In the present article, 12 small molecules of 2‐benzylidenehydrazine‐1‐carbothioamide were designed, synthesized and evaluated for their anti‐tyrosinase activities followed by molecular docking and pharmacophore‐based screening. Among synthesized thiosemicarbazone derivatives, one compound, (2E)‐2‐[(4‐nitrophenyl)methylidene]hydrazine‐1‐carbothioamide, is the strongest inhibitor of mushroom tyrosinase with IC50 of 0.05 μM which demonstrated a 128‐fold increase in potency compared to the positive control. Kinetic studies also revealed mix type inhibition by this compound. Docking studies confirmed the complete fitting of the synthesized compounds into the tyrosinase active site. The results underline the potential of 2‐benzylidenehydrazine‐1‐carbothioamides as potent pharmacophore to extend the tyrosinase inhibition in drug discovery. 相似文献
33.
Aida Rieko Hagiwara Keitaro Okano Kazunori Nakata Kyoko Obata Yuho Yamashita Takahiro Yoshida Kaoru Hagiwara Hiromi 《Molecular biology reports》2021,48(3):2291-2297
Molecular Biology Reports - Apigenin is a flavonoid with antioxidant and anticancer effects. It has been reported that apigenin inhibits proliferation, migration, and invasion and induces apoptosis... 相似文献
34.
35.
Massimo Collino Mara Rogazzo Alessandro Pini Elisa Benetti Arianna Carolina Rosa Fausto Chiazza Roberto Fantozzi Daniele Bani Emanuela Masini 《Journal of cellular and molecular medicine》2013,17(11):1494-1505
Although recent preclinical and clinical studies have demonstrated that recombinant human relaxin (rhRLX) may have important therapeutic potential in acute heart failure and chronic kidney diseases, the effects of acute rhRLX administration against renal ischaemia/reperfusion (I/R) injury have never been investigated. Using a rat model of 1‐hr bilateral renal artery occlusion followed by 6‐hr reperfusion, we investigated the effects of rhRLX (5 μg/Kg i.v.) given both at the beginning and after 3 hrs of reperfusion. Acute rhRLX administration attenuated the functional renal injury (increase in serum urea and creatinine), glomerular dysfunction (decrease in creatinine clearance) and tubular dysfunction (increase in urinary excretion of N‐acetyl‐β‐glucosaminidase) evoked by renal I/R. These beneficial effects were accompanied by a significant reduction in local lipid peroxidation, free radical‐induced DNA damage and increase in the expression/activity of the endogenous antioxidant enzymes Mn‐ and CuZn‐superoxide dismutases (SOD). Furthermore, rhRLX administration attenuated the increase in leucocyte activation, as suggested by inhibition of myeloperoxidase activity, intercellular‐adhesion‐molecule‐1 expression, interleukin (IL)‐1β, IL‐18 and tumour necrosis factor‐α production as well as increase in IL‐10 production. Interestingly, the reduced oxidative stress status and neutrophil activation here reported were associated with rhRLX‐induced activation of endothelial nitric oxide synthase and up‐regulation of inducible nitric oxide synthase, possibly secondary to activation of Akt and the extracellular signal‐regulated protein kinase (ERK) 1/2, respectively. Thus, we report herein that rhRLX protects the kidney against I/R injury by a mechanism that involves changes in nitric oxide signalling pathway. 相似文献
36.
Hojjatollah Nazari Asieh Heirani-Tabasi Maryam Hajiabbas Milad Salimi Bani Mahnaz Nazari Vahid Pirhajati Mahabadi Iman Rad Mousa Kehtari Seyed Hossein Ahmadi Tafti Masoud Soleimani 《Journal of cellular biochemistry》2020,121(4):2981-2993
Mimicking the structure of extracellular matrix (ECM) of myocardium is necessary for fabrication of functional cardiac tissue. The superparamagnetic iron oxide nanoparticles (SPIONs, Fe3O4), as new generation of magnetic nanoparticles (NPs), are highly intended in biomedical studies. Here, SPION NPs (1 wt%) were synthesized and incorporated into silk-fibroin (SF) electrospun nanofibers to enhance mechanical properties and topography of the scaffolds. Then, the mouse embryonic cardiac cells (ECCs) were seeded on the scaffolds for in vitro studies. The SPION NPs were studied by scanning electron microscope (SEM), X-ray diffraction (XRD), and transmission electron microscope (TEM). SF nanofibers were characterized after incorporation of SPIONs by SEM, TEM, water contact angle measurement, and tensile test. Furthermore, cytocompatibility of scaffolds was confirmed by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. SEM images showed that ECCs attached to the scaffolds with elongated morphologies. Also, the real-time PCR and immunostaining studies approved upregulation of cardiac functional genes in ECCs seeded on the SF/SPION-casein scaffolds including GATA-4, cardiac troponin T, Nkx 2.5, and alpha-myosin heavy chain, compared with the ones in SF. In conclusion, incorporation of core-shells in SF supports cardiac differentiation, while has no negative impact on ECCs' proliferation and self-renewal capacity. 相似文献
37.
Arnab Kumar Maity Anirban Bhattacharya Bani K. Mallick Veerabhadran Baladandayuthapani 《Biometrics》2020,76(1):316-325
Accurate prognostic prediction using molecular information is a challenging area of research, which is essential to develop precision medicine. In this paper, we develop translational models to identify major actionable proteins that are associated with clinical outcomes, like the survival time of patients. There are considerable statistical and computational challenges due to the large dimension of the problems. Furthermore, data are available for different tumor types; hence data integration for various tumors is desirable. Having censored survival outcomes escalates one more level of complexity in the inferential procedure. We develop Bayesian hierarchical survival models, which accommodate all the challenges mentioned here. We use the hierarchical Bayesian accelerated failure time model for survival regression. Furthermore, we assume sparse horseshoe prior distribution for the regression coefficients to identify the major proteomic drivers. We borrow strength across tumor groups by introducing a correlation structure among the prior distributions. The proposed methods have been used to analyze data from the recently curated “The Cancer Proteome Atlas” (TCPA), which contains reverse-phase protein arrays–based high-quality protein expression data as well as detailed clinical annotation, including survival times. Our simulation and the TCPA data analysis illustrate the efficacy of the proposed integrative model, which links different tumors with the correlated prior structures. 相似文献
38.
Sara Zalghout Abdullah Kaplan Emna Abidi Ghewa A. El-Achkar Wared Nour-Eldine Asmaa A. Khalil Firas Kobeissy Ahmad Husari Aida Habib Fouad A. Zouein Eva Hamade 《Journal of cellular physiology》2020,235(2):1568-1575
Despite increased social awareness, marketing restraints, tobacco taxation, and available smoking cessation rehab programs, active and passive smoking remain a worldwide challenging epidemic and a key risk factor for cardiovascular diseases development. Although cardiovascular (CV) protection is more pronounced in women than in men due to estrogenic effects, tobacco cigarette smoking exposure seems to alter this protection by modulating estrogen actions via undefined mechanisms. Premenopausal cigarette smoking women are at higher risk of adverse CV effects than non-smokers. In this study, we investigated the impact of cigarette smoking on early CV injury after myocardial infarction (MI) in non-menopausal female mice. Aortic arch calcification, fibrosis, reactive oxygen species, and gene expression of inflammatory and calcification genes were exaggerated in mice exposed to cigarette smoke (CS). These findings suggest that aortic injury following MI, characterized by vascular smooth muscle cells transdifferentiation, calcification, inflammation, and collagen deposition but not cardiac dysfunction is exacerbated with CS exposure. The novel findings of this study highlight the importance of aortic injury on short and long-term prognosis in CS-exposed MI females. Linking those findings to estrogen alteration is probable and entails investigation. 相似文献
39.
Namik Kaya Dilek Colak Albandary Al-Bakheet Banan Al-Younes Sahar Tulbah Maha Daghestani Fuad Al-Mutairi Mohammed Al-Amoudi Ali Al-Odaib Aida I. Al-Aqeel 《Gene》2013
Isovaleric acidemia (IVA) is a rare autosomal recessive disorder caused by a deficiency of isovaleryl-CoA dehydrogenase encoded by IVD gene. In this case study we report the first Saudi IVA patients from a consanguineous family with a novel transversion (p.G362V) and briefly discuss likely phenotype–genotype correlation of the disease in the Saudi population. We explored the functional consequences of the mutation by using various bioinformatics prediction algorithms and discussed the likely mechanism of the disease caused by the mutation. 相似文献
40.
Ibtissem Ben Amara Aida Karray Ahmed Hakim Yassine Ben Ali Afef Troudi Nejla Soudani Tahia Boudawara Khaled Mounir Zeghal Najiba Zeghal 《Biological trace element research》2013,156(1-3):230-242
Dimethoate (DM) is an organophosphate insecticide widely used in agriculture and industry and has toxic effects on non-target organisms especially mammalian. However, we still know little about DM-induced kidney injury and its alleviation by natural antioxidants. In the present study, selenium (Se), vitamin E, DM, Se+DM, vitamin E+DM, Se+vitamin E+DM were given to adult rats for 4 weeks. Plasma creatinine and uric acid, kidney MDA, PC, H2O2 and AOPP levels were higher, while Na+-K+-ATPase and LDH values were lower in the DM group than those of controls. A smear without ladder formation on agarose gel was shown in the DM group, indicating random DNA degradation and DM-induced genotoxicity. A decrease in kidney GSH, NPSH and plasma urea levels and an increase in GPx, SOD and catalase activities were observed in the DM group when compared to those of controls. Plasma cystatin C levels increased, indicating a decrease in glomerular filtration rate. When Se or vitamin E was added through diet, the biochemical parameters cited above were partially restored in Se+DM and vitamin E+DM than DM group. The joint effect of Se and vitamin E was more powerful against DM-induced oxidative stress and kidney dysfunction. The changes in biochemical parameters were substantiated by histological data. In conclusion, our results indicated a possible mechanism of DM-induced nephrotoxicity, where renal genotoxicity was noted, membrane-bound ATPases and plasma biomarkers were disturbed. Se and vitamin E ameliorated the toxic effects of this pesticide in renal tissue suggesting their role as potential antioxidants. 相似文献