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在高中生物教学中,血糖平衡的调节一直是重要的教学内容。以往的教学设计思路主要是依靠教师讲述,学生被动接受,因此学生在学习上缺乏主动性。且由于内容比较抽象,学生很难真正理解。教师如何依据现代教育理论,通过组织和引导学生模拟血糖的调节机制,建构和不断修正动态的物理模型,再建构抽象的血糖调节的图解式概念模型,从而使学生深入理解血糖调节的机制,更好地理解体内激素对生命活动进行的调节,不仅是突破教学难点有效途径,对学生建立科学思维方式也具有重要的意义。结合课堂教学实际,介绍“建立血糖调节模型”的教学设计和“概念模型”的教学组织策略两个方面研究成果。 相似文献
3.
《Bioorganic & medicinal chemistry letters》2014,24(19):4714-4723
Use of the tools of SBDD including crystallography led to the discovery of novel and potent 6,5 heterobicyclic MEKi’s [J. Med. Chem. 2012, 55, 4594]. The core change from a 5,6 heterobicycle to a 6,5 heterobicycle was driven by the desire for increased structural diversity and aided by the co-crystal structure of G-925 [J. Med. Chem. 2012, 55, 4594]. The key design feature was the shift of the attachment of the five-membered heterocyclic ring towards the B ring while maintaining the key hydroxamate and anilino pharamcophoric elements in a remarkably similar position as in G-925. From modelling, changing the connection point of the five membered ring heterocycle placed the H-bond accepting nitrogen within a good distance and angle to the Ser212 [J. Med. Chem. 2012, 55, 4594]. The resulting novel 6,5 benzoisothiazole MEKi G-155 exhibited improved potency versus aza-benzofurans G-925 and G-963 but was a potent inhibitor of cytochrome P450’s 2C9 and 2C19. Lowering the log D by switching to the more polar imidazo[1,5-a] pyridine core significantly diminished 2C9/2C19 inhibition while retaining potency. The imidazo[1,5-a] pyridine G-868 exhibited increased potency versus the starting point for this work (aza-benzofuran G-925) leading to deprioritization of the azabenzofurans. The 6,5-imidazo[1,5-a] pyridine scaffold was further diversified by incorporating a nitrogen at the 7 position to give the imidazo[1,5-a] pyrazine scaffold. The introduction of the C7 nitrogen was driven by the desire to improve metabolic stability by blocking metabolism at the C7 and C8 positions (particularly the HLM stability). It was found that improving on G-868 (later renamed GDC-0623) required combining C7 nitrogen with a diol hydroxamate to give G-479. G-479 with polarity distributed throughout the molecule was improved over G-868 in many aspects. 相似文献
4.
Henryk Brzeskwiniewicz 《Biometrical journal. Biometrische Zeitschrift》1995,37(2):191-198
We present the idea of using multiresponse incomplete block designs when not all responses can be observed in all experimental units. For a special class of such designs, in which partial designs are PBB designs, a method for estimating natural treatment contrast is given. We also consider the problem of testing the hypotheses concerning the natural and any estimable treatment contrasts. For testing this hypothesis the Wald statistics, being asymptotically chi-square distributed, is proposed. 相似文献
5.
Mitsunori Kono Tsuneo Oda Michiko Tawada Takashi Imada Yoshihiro Banno Naohiro Taya Tetsuji Kawamoto Hidekazu Tokuhara Yoshihide Tomata Naoki Ishii Atsuko Ochida Yoshiyuki Fukase Tomoya Yukawa Shoji Fukumoto Hiroyuki Watanabe Keiko Uga Akira Shibata Hideyuki Nakagawa Satoshi Yamamoto 《Bioorganic & medicinal chemistry》2018,26(2):470-482
A series of tetrahydroisoquinoline derivatives were designed, synthesized, and evaluated for their potential as novel orally efficacious retinoic acid receptor-related orphan receptor-gamma t (RORγt) inverse agonists for the treatment of Th17-driven autoimmune diseases. We carried out cyclization of the phenylglycinamide core by structure-based drug design and successfully identified a tetrahydroisoquinoline carboxylic acid derivative 14 with good biochemical binding and cellular reporter activity. Interestingly, the combination of a carboxylic acid tether and a central fused bicyclic ring was crucial for optimizing PK properties, and the compound 14 showed significantly improved PK profile. Successive optimization of the carboxylate tether led to the discovery of compound 15 with increased inverse agonistic activity and an excellent PK profile. Oral treatment of mice with compound 15 robustly and dose-dependently inhibited IL-17A production in an IL23-induced gene expression assay. 相似文献
6.
The generally positive relationship between biodiversity of groups of directly or indirectly interacting organisms is one of the most important ecological concepts (Gaston, 2000 Nature, 405 , 220–227; Scherber C, Eisenhauer N, Weisser WW et al., 2010 Nature, 468 , 553–556). In a recent issue of Molecular Ecology, Gao C, Shi N‐N, Liu Y‐X et al. (2013: 22 , 3403–3414) reported that the richness of plants and ectomycorrhizal fungi is positively correlated both at local and at global scales. Here, we challenge these findings by re‐analysis of data and ascribe the reported results to sampling effect and poor data compilation. 相似文献
7.
I. Siatkowski 《Biometrical journal. Biometrische Zeitschrift》1993,35(3):283-289
For some subclass of a two-way elimination of heterogeneity design, necessary and sufficient conditions are established for row-connectedness and column-connectedness of a design to imply its connectedness. 相似文献
8.
Yulong He Huixia Dou Dingding Gao Ting Wang Mingming Zhang Heyao Wang Yingxia Li 《Bioorganic & medicinal chemistry》2019,27(19):115015
Fatty acid binding protein 4 (FABP4) and fatty acid binding protein 5 (FABP5) are mainly expressed in adipocytes and/or macrophages and play essential roles in energy metabolism and inflammation. When FABP4 function is diminished, FABP5 expression is highly increased possibly as a functional compensation. Dual FABP4/5 inhibitors are expected to provide beneficial synergistic effect on treating diabetes, atherosclerosis, and inflammation-related diseases. Starting from our previously reported selective FABP4 inhibitor 8, structural biology information was used to modulate the selectivity profile and to design potent dual FABP4/5 inhibitors with good selectivity against FABP3. Two compounds A16 and B8 were identified to show inhibitory activities against both FABP4/5 and good selectivity over FABP3, which could also reduce the level of forskolin-stimulated lipolysis in mature 3T3-L1 adipocytes. Compared with compound 8, these two compounds exhibited better anti-inflammatory effects in lipopolysaccharide-stimulated RAW264.7 murine macrophages, with decreased levels of pro-inflammatory cytokines TNFα and MCP-1 and apparently inhibited IKK/NF-κB pathway. 相似文献
9.
肝素和硫酸乙酰肝素是一类应用于临床抗凝血的糖胺聚糖。肝素葡萄糖醛酸C5异构酶(Heparosan-N-sulfate-glucuronate 5-epimerase,C5,EC 5.1.3.17) 是肝素和硫酸乙酰肝素合成过程中重要的修饰酶,催化N-硫酸化肝素前体 (N-sulfoheparosan) 的D-葡萄糖醛酸 (D-GlcA) 上5号位羧基翻转生成L-艾杜糖醛酸 (L-iduronic acid,L-IdoA)。文中以大肠杆菌Escherichia coli为宿主对斑马鱼来源的肝素葡萄糖醛酸C5异构酶基因Glce进行重组表达优化与分子改造。比较了3种不同的表达载体pET20b(+)、pET28a(+) 和pCold Ⅲ对C5表达的差异情况,其中以嗜冷启动型载体pCold Ⅲ表达酶活最高,达到(1 873.61±5.42) U/L。为了进一步提高C5的可溶表达量,在N端融合促溶标签SET2后,可溶蛋白表达量比对照提高了50%,酶活达到 (2 409.25±6.43) U/L。在此基础上,通过理性设计对底物结合口袋进行定点突变,获得最优突变体 (V153R) 的酶活和比酶活分别为 (5 804.32±5.63) U/L和(145.14±2.33) U/mg,是原始酶的2.41倍和2.28倍。肝素C5异构酶改造与表达优化为酶法催化合成肝素奠定了基础。 相似文献
10.
饲养条件对黄粉虫幼虫生长及存活的影响 总被引:15,自引:1,他引:14
采用5因素2次正交旋转组合设计,以黄粉虫幼虫饲养过程中饲养温度(X1)、相对湿度(X2)、虫粪筛除频率(X3)、饲养密度(X4)以及饲料含水量(X5)5因素为参试因素,考查它们对黄粉虫高龄幼虫的生长及存活的影响,建立并进行了简化得到了以黄粉虫幼虫增重率及死亡率为目标函数的回归模型:Y增=127.5079 18.6559x5 2.7894x3x4-2.3854x3x5-3.0594x1^2 1.824lx3^2-3.8559x5^2;y死=1.7459 0.4l08x1 0.0975x2 0.9025x4 0.3442x5 0.0834x1^2 0.3060x4^2-0.2623x5^2。分析结果表明:影响黄粉虫幼虫生长后期增重及死亡的主要因素分别为饲料含水量和饲养密度;饲料含水量和温度对黄粉虫增重有着重要的影响,饲养密度、温度、饲料含水量对黄粉虫的死亡有着重要的影响,其影响均达1%或5%显著水平;推荐的饲养条件为:温度24—27℃、相对湿度64%一70%、筛粪频率2—4d/次、饲养密度0.42-0.49g/cm^2、饲料含水量l3.48%-l7.48%。 相似文献