全文获取类型
收费全文 | 668篇 |
免费 | 45篇 |
出版年
2024年 | 2篇 |
2023年 | 5篇 |
2022年 | 14篇 |
2021年 | 25篇 |
2020年 | 11篇 |
2019年 | 10篇 |
2018年 | 20篇 |
2017年 | 13篇 |
2016年 | 24篇 |
2015年 | 28篇 |
2014年 | 32篇 |
2013年 | 37篇 |
2012年 | 66篇 |
2011年 | 65篇 |
2010年 | 45篇 |
2009年 | 33篇 |
2008年 | 46篇 |
2007年 | 37篇 |
2006年 | 43篇 |
2005年 | 16篇 |
2004年 | 30篇 |
2003年 | 27篇 |
2002年 | 13篇 |
2001年 | 5篇 |
1999年 | 4篇 |
1998年 | 8篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 4篇 |
1994年 | 6篇 |
1992年 | 4篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1971年 | 1篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1966年 | 2篇 |
1965年 | 1篇 |
1964年 | 1篇 |
1962年 | 1篇 |
1961年 | 1篇 |
排序方式: 共有713条查询结果,搜索用时 15 毫秒
101.
Mourad Said Eric Battaglia Abdelaziz Elass Virginie Cano Jean-Claude Ziegler Alain Cartier Marie-Hlne Livertoux Grard Vergoten Sylvie Fournel-Gigleux Jacques Magdalou 《Journal of biochemical and molecular toxicology》1998,12(1):19-27
A series of potent and competitive inhibitors of UDP-glucuronosyltransferase derived from 7,7,7-triphenylheptanoic acid has been synthesized in order to probe the active site of the isozyme involved in the glucuronidation of the endogenous toxic compound, bilirubin IXα. Like triphenylalkylcarboxylic acids, triphenyl alcohols were found to be very effective competitive inhibitors of the reaction (Ki 12 to 180 μM). Superimposition of the best inhibitors with bilirubin by computer modeling showed a marked spatial similarity, which accounts for the observed competitive-type inhibition. The bulky triphenylmethyl moiety of the inhibitor superimposed well on the part of the bilirubin molecule containing three of the four pyrrole rings. In agreement, substitution of the triphenylmethyl moiety by planar structures such as fluorenyl or indenyl rings completely suppressed the inhibition. In addition, the weak inhibition exerted by the shortest carboxylic acids could be related to the higher acidity of these molecules. The inhibition potency depended on the acidity of the molecules; the more acidic, the less inhibitory, suggesting that the presence of a negative charge on the inhibitor molecule prevents bilirubin glucuronidation. Based on these results, a reaction mechanism for bilirubin glucuronidation is postulated. © 1997 John Wiley & Sons, Inc. J Biochem Toxicol 12: 19–27, 1998 相似文献
102.
Fatma Farrag Ali Mostafa Mourad Mohammed Youssef Hussein Manar Fouli Gaber Ibrahim 《Cell biochemistry and function》2024,42(1):e3938
The liver is an important organ, and hepatic ischemia–reperfusion (IR) injury is a frequent pathophysiological process that can cause significant morbidity and mortality. Thus, our study aimed to investigate the effect of targeting PI3K/p-Akt/eNOS (phosphoinositide 3-kinase/phospho-protein kinase B/endothelial nitric oxide synthase), Nrf2/HO-1 (nuclear factor-erythroid 2-related factor-2/heme oxygenase-1), and NF-κB/p53 (nuclear factor-κB/tumor protein 53) signaling pathways by using angiotensin (1–7) [ang-(1–7)] against hepatic injury induced by IR. Thirty-two male rats were included in sham group, ang-(1–7)-treated group, hepatic IR group, and hepatic IR group treated with ang-(1–7). The levels of hepatic ang-(1–7), angiotensin II (Ang II), angiotensin-converting enzyme 2 (ACE2), HO-1, malondialdehyde (MDA), PI3K, and p-Akt were assessed. The expressions of eNOS and B-cell leukemia/lymphoma-2 (BCL-2) in the liver were determined. Histological assessment and immunohistochemical expression of NF-κB, p53, and Nrf2 were carried out. The levels of reduced glutathione (GSH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in serum were estimated. Results showed that administration of ang-(1–7) to hepatic IR rats led to significant amelioration of hepatic damage through a histological evaluation that was associated with significant upregulation of the expressions of PI3K/p-Akt/eNOS and Nrf2/HO-1 with downregulation of NF-κB/p53 signaling pathways. In conclusion, PI3K/p-Akt/eNOS and Nrf2/HO-1 signaling pathways are involved in the protective effects of ang-(1–7) against hepatic damage induced by IR. Therefore, ang-(1–7) can be used to prevent hepatic IR, which occurs in certain conditions such as liver transplantation, hemorrhagic shock, and severe infection. 相似文献
103.
Mourad Hadj Slimen Hammadi Fakhfakh Mohamed Gassara Sofiane Kechaou Ali Bahloul Mohamed Nabil Mhiri 《Andrologie》2008,18(4):264-273
Introduction
Priapism is a prolonged, painful and persistent erection, unrelated to sexual stimulation. The management of priapism is complex and requires various medical or surgical treatments. The authors review the aetiology, treatment and outcome of priapism.Material and methods
26 cases of low-flow priapism were collected over a period of 23 years (1985–2007), corresponding to 22 adults and 4 children (average age: 32 years) with various types of priapism. The time to appropriate management after onset of priapism varied according to the aetiology and the time to consultation (range: 16 hours to 15 days).Results
Complete and persistent detumescence for the first 24 hours was obtained in 84% of cases, sometimes with multiple successive procedures. No case of early recurrence was observed. 21 patients were regularly followed for a period of 3 months to 10 years (mean follow-up: 2 years). There were 9 (42.9%) successes (recovery of normal erectile function), 4 partial results (19%) and 9 (30.1%) failures (complete erectile dysfunction).Conclusion
Low-flow priapism must be considered to be a serious andrological emergency. Medical treatment can be effective in early forms, but surgery must not be delayed to prevent permanent erectile dysfunction secondary to extensive corpora cavernosa fibrosis. 相似文献104.
Bradley M Alexander L Duncan K Chennaoui M Jones AC Sánchez-Martín RM 《Bioorganic & medicinal chemistry letters》2008,18(1):313-317
Intracellular pH in living cells is measured in real time at the single cell level using fluorescently covalently loaded microspheres as efficient carrier systems and stable sensors. The use of these sensors immobilized covalently onto polymeric particles allows analysis of intracellular pH flux over long period of time and eliminates the disadvantages such as dilution within the cell, elimination via leakage or compartmentalization. 相似文献
105.
106.
Walid Rachidi Fabrice Chimienti Mhammed Aouffen Abderrahmane Senator Pascale Guiraud Michel Seve Alain Favier 《Journal of trace elements in medicine and biology》2009,23(3):214-223
PrPC contains several octapeptide repeats sequences toward the N-terminus which have binding affinity for divalent metals such as copper, zinc, nickel and manganese. However, the link between PrPC expression and zinc metabolism remains elusive. Here we studied the relationship between PrPC and zinc ions intracellular homeostasis using a cell line expressing a doxycycline-inducible PrPC gene. No significant difference in 65Zn2+ uptake was observed in cells expressing PrPC when compared with control cells. However, PrPC-expressing cells were more resistant to zinc-induced toxicity, suggesting an adaptative mechanism induced by PrPC. Using zinquin-ethyl-ester, a specific fluorophore for vesicular free zinc, we observed a significant re-localization of intracellular exchangeable zinc in vesicles after PrPC expression. Finally, we demonstrated that PrPC expression induces metallothionein (MT) expression, a zinc-upregulated zinc-binding protein. Taken together, these results suggest that PrPC modifies the intracellular localization of zinc rather than the cellular content and induces MT upregulation. These findings are of major importance since zinc deregulation is implicated in several neurodegenerative disorders. It is postulated that in prion diseases the conversion of PrPC to PrPSc may deregulate zinc homeostasis mediated by metallothionein. 相似文献
107.
Mourad Chioua Abdelouahid Samadi Elena Soriano Olivier Lozach Laurent Meijer José Marco-Contelles 《Bioorganic & medicinal chemistry letters》2009,19(16):4566-4569
The synthesis and biological evaluation of a number of differently substituted 3,6-diamino-1H-pyrazolo[3,4-b]pyridine derivatives are reported. From the inhibition results on a selection of disease-relevant protein kinases [IC50 (μM) DYRK1A = 11; CDK5 = 0.41; GSK-3 = 1.5] we have observed that 3,6-diamino-4-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4) constitutes a potential new and simple lead compound in the search of drugs for the treatment of Alzheimer’s disease. 相似文献
108.
109.
Krishna Jafa Peter McElroy Lisa Fitzpatrick Craig B. Borkowf Robin MacGowan Andrew Margolis Ken Robbins Ae Saekhou Youngpairoj Dale Stratford Alan Greenberg Jennifer Taussig R. Luke Shouse Madeleine LaMarre Eleanor McLellan-Lemal Walid Heneine Patrick S. Sullivan 《PloS one》2009,4(5)
Introduction
HIV prevalence among state prison inmates in the United States is more than five times higher than among nonincarcerated persons, but HIV transmission within U.S. prisons is sparsely documented. We investigated 88 HIV seroconversions reported from 1988–2005 among male Georgia prison inmates.Methods
We analyzed medical and administrative data to describe seroconverters'' HIV testing histories and performed a case-crossover analysis of their risks before and after HIV diagnosis. We sequenced the gag, env, and pol genes of seroconverters'' HIV strains to identify genetically-related HIV transmission clusters and antiretroviral resistance. We combined risk, genetic, and administrative data to describe prison HIV transmission networks.Results
Forty-one (47%) seroconverters were diagnosed with HIV from July 2003–June 2005 when voluntary annual testing was offered. Seroconverters were less likely to report sex (OR [odds ratio] = 0.02, 95% CI [confidence interval]: 0–0.10) and tattooing (OR = 0.03, 95% CI: <0.01–0.20) in prison after their HIV diagnosis than before. Of 67 seroconverters'' specimens tested, 33 (49%) fell into one of 10 genetically-related clusters; of these, 25 (76%) reported sex in prison before their HIV diagnosis. The HIV strains of 8 (61%) of 13 antiretroviral-naïve and 21 (40%) of 52 antiretroviral-treated seroconverters were antiretroviral-resistant.Discussion
Half of all HIV seroconversions were identified when routine voluntary testing was offered, and seroconverters reduced their risks following their diagnosis. Most genetically-related seroconverters reported sex in prison, suggesting HIV transmission through sexual networks. Resistance testing before initiating antiretroviral therapy is important for newly-diagnosed inmates. 相似文献110.