全文获取类型
收费全文 | 109篇 |
免费 | 7篇 |
出版年
2023年 | 2篇 |
2022年 | 4篇 |
2021年 | 11篇 |
2020年 | 2篇 |
2019年 | 5篇 |
2018年 | 2篇 |
2017年 | 5篇 |
2016年 | 3篇 |
2015年 | 3篇 |
2014年 | 2篇 |
2013年 | 8篇 |
2012年 | 12篇 |
2011年 | 11篇 |
2010年 | 4篇 |
2009年 | 8篇 |
2008年 | 5篇 |
2007年 | 9篇 |
2006年 | 4篇 |
2005年 | 2篇 |
2004年 | 1篇 |
2002年 | 2篇 |
2001年 | 1篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1997年 | 1篇 |
1991年 | 2篇 |
1989年 | 1篇 |
1985年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1977年 | 1篇 |
排序方式: 共有116条查询结果,搜索用时 125 毫秒
101.
Karginov VA Yohannes A Robinson TM Fahmi NE Alibek K Hecht SM 《Bioorganic & medicinal chemistry》2006,14(1):33-40
Recently, we demonstrated that simultaneous blocking of bacterial growth by antibiotics and inhibition of anthrax toxin action with antibodies against protective antigen were beneficial for the treatment of anthrax. The present study examined the hypothesis that blocking the pore formed by protective antigen can inhibit the action of anthrax toxin. The potential inhibitors were chosen by a structure-based design using beta-cyclodextrin as the starting molecule. Several beta-cyclodextrin derivatives were evaluated for their ability to protect RAW 264.7 cells from the action of anthrax lethal toxin. Per-substituted aminoalkyl derivatives displayed inhibitory activity and were protective against anthrax lethal toxin action at low micromolar concentrations. These results provide the basis for a structure-based drug discovery program, with the goal of identifying new drug candidates for anthrax treatment. 相似文献
102.
The glyoxalase system catalyzes the conversion of toxic methylglyoxal to nontoxic d-lactic acid using glutathione (GSH) as a coenzyme. Glyoxalase II (GlxII) is a binuclear Zn enzyme that catalyzes the second step of this conversion, namely the hydrolysis of S-d-lactoylglutathione, which is the product of the Glyoxalase I (GlxI) reaction. In this paper we use density functional theory method to investigate the reaction mechanism of GlxII. A model of the active site is constructed on the basis of the X-ray crystal structure of the native enzyme. Stationary points along the reaction pathway are optimized and the potential energy surface for the reaction is calculated. The calculations give strong support to the previously proposed mechanism. It is found that the bridging hydroxide is capable of performing nucleophilic attack at the substrate carbonyl to form a tetrahedral intermediate. This step is followed by a proton transfer from the bridging oxygen to Asp58 and finally C-S bond cleavage. The roles of the two zinc ions in the reaction mechanism are analyzed. Zn2 is found to stabilize the charge of tetrahedral intermediate thereby lowering the barrier for the nucleophilic attack, while Zn1 stabilizes the charge of the thiolate product, thereby facilitating the C-S bond cleavage. Finally, the energies involved in the product release and active-site regeneration are estimated and a new possible mechanism is suggested. 相似文献
103.
Fahmi A 《Journal of biotechnology》2010,156(4):364-369
South Asia, once considered as a laggard, has grown at about 6% on average over the past two decades and the current growth outlook is much brighter. However, this growth is not always well distributed and the challenges of institutionalising policies and mechanisms to ensure inclusive growth are now being seriously considered by these countries governments. The targets set by south Asian countries are primarily based on the investments in infrastructural sector with an objective to generate educated and skilled human resources. The other most important inclusive growth area is the core public services; Agriculture, Health, and Energy, which are increasingly becoming technology driven. Biotechnology has been increasingly seen now to be an area of technology that holds the greatest new potential to address problems arising from low productivity, overburdened health systems, high-cost unsustainable energy supplies and the need for developing new materials for industrial and environmental applications. This article attempts to highlight perspectives on some of the emerging areas of biotechnology that have good potential for economic development in the context of south Asia, as well as discuss briefly some of UNESCO's initiatives in biotechnology for that region. 相似文献
104.
105.
Archives of Microbiology - The study focuses on the impact of foliar spraying cyanobacterium Spirulina platensis extract and the inoculation with the endophyte N2-fixing Pseudomonas stutzeri, and... 相似文献
106.
Polina Georgieva Qian Wu Michael J. McLeish Fahmi Himo 《Biochimica et Biophysica Acta - Proteins and Proteomics》2009,1794(12):1831-1837
Hybrid density functional theory methods were used to investigate the reaction mechanism of human phenylethanolamine N-methyltransferase (hPNMT). This enzyme catalyzes the S-adenosyl-l-methionine-dependent conversion of norepinephrine to epinephrine, which constitutes the terminal step in the catecholamine biosynthesis. Several models of the active site were constructed based on the X-ray structure. Geometries of the stationary points along the reaction path were optimized and the reaction barrier and energy were calculated and compared to the experimental values. The calculations demonstrate that the reaction takes place via an SN2 mechanism with methyl transfer being rate-limiting, a suggestion supported by mutagenesis studies. Optimal agreement with experimental data is reached using a model in which both active site glutamates are protonated. Overall, the mechanism of hPNMT is more similar to those of catechol O-methyltransferase and glycine N-methyltransferase than to that of guanidinoacetate N-methyltransferase in which methyl transfer is coupled to proton transfer. 相似文献
107.
108.
The conditions for the sulfhydryl oxidase (SOX) production and activity from an Egyptian isolate of Aspergillus niger were optimized. Purification and determination of the kinetic properties (K
m and V
max) of the purified enzyme have been done. The possibility for the SOX induction using L-Cys (as a natural substrate) was studied
to determine whether SOX could be produced as an inducible enzyme in addition to being a constitutive one (i.e. whether induction
leads to increase SOX production and activity or not). The optimum temperature and pH for its activity were found to be 60°C
and 5.5, respectively. The activity of the induced intracellular SOX, was measured according to Ellman’s method using the
standard GSH oxidation where it reached 94% while that of non-induced one reached only 27.6%. This wide difference in activity
between the induced and non-induced SOX indicates the successful L—Cys-induction of the SOX production (i.e. SOX from A. niger AUMC 4947 is an inducible enzyme). Molecular characterization of the pure SOX revealed that it is constituted of two 50–55
KDa subunits. K
m and V
max were found to be 6.0 mM and 100 μM/min/mg respectively. 相似文献
109.
Abdelgawad A. Fahmi Mohamed A. El Raey Abeer Y. Ibrahim Mohamed A.O. Abdelfattah Abeer M Abdelmageed Mansour Sobeh 《Saudi Journal of Biological Sciences》2021,28(5):3117-3125
Cancer is the second leading cause of mortality accounting for one in every six deaths globally. Plant secondary metabolites, among them polyphenols, represent an effective and much safer alternative approach to the currently available medications. In this work, utilizing LC-MS/MS, we characterized the constituents of S. yapa leaves extract and evaluated its antioxidant and anticancer properties. In total, 34 secondary metabolites, mainly flavonoids (Tricin, luteolin, and apigenin and their glucosides as well as sulfated derivatives) were identified. The extract manifested substantial antioxidant activity in DPPH assay, and high total phenolic content determined by Folin Ciocalteu method. The extract was safe up to 4800 mg/kg b.wt. when administered orally in mice and neither affected the hematological parameters nor the liver enzyme levels at the studied dose (LD50, 480 mg, kg b.wt.). In the treated animals, the extract surpassed the reference drug (5-flouro uracil) and significantly reduced the tumor volume and weight by 71.50 and 85.46%, respectively, increased the median survival time to 53.2 days and the lifespan by 116%. The extract improved all the hematological parameters, where it increased the hemoglobin (Hb) concentration, red blood cell (RBC) count, packed cell volume (PVC) and platelets by 58.21, 8.98, 9.89 and 120%, respectively, compared to the untreated EAC bearing animals. Additionally, the extract significantly declined the elevated levels of ALT and AST enzymes by 29.18% and 59.88%, respectively. In molecular docking, the annotated flavonoids displayed appreciable binding affinities to the active sites of VEGFR1 and VEGFR2. In conclusion, Saba yapa is a promising plant that can be introduced to further advanced clinical studies for the development of novel anticancer drugs with lower side effects. 相似文献
110.
Rani Sasidharan Bo Hyun Eom Jeong Hyun Heo Jong Eun Park Mohamed A. Abdelgawad Arafa Musa Nicola Gambacorta Orazio Nicolotti Sreedharannair Leelabaiamma Manju Bijo Mathew Hoon Kim 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):188
Nine compounds (MO1–MO9) containing the morpholine moiety were assessed for their inhibitory activities against monoamine oxidases (MAOs) and acetylcholinesterase (AChE). Most of the compounds potently inhibited MAO-B; MO1 most potently inhibited with an IC50 value of 0.030 µM, followed by MO7 (0.25 µM). MO5 most potently inhibited AChE (IC50 = 6.1 µM), followed by MO9 (IC50 = 12.01 µM) and MO7 most potently inhibited MAO-A (IC50 = 7.1 µM). MO1 was a reversible mixed-type inhibitor of MAO-B (Ki = 0.018 µM); MO5 reversibly competitively inhibited AChE (Ki = 2.52 µM); and MO9 reversibly noncompetitively inhibited AChE (Ki = 7.04 µM). MO1, MO5 and MO9 crossed the blood–brain barrier, and were non-toxic to normal VERO cells. These results show that MO1 is a selective inhibitor of MAO-B and that MO5 is a dual-acting inhibitor of AChE and MAO-B, and that both should be considered candidates for the treatment of Alzheimer’s disease. 相似文献