首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   386篇
  免费   28篇
  国内免费   71篇
  2024年   1篇
  2023年   19篇
  2022年   21篇
  2021年   32篇
  2020年   33篇
  2019年   25篇
  2018年   32篇
  2017年   20篇
  2016年   21篇
  2015年   32篇
  2014年   39篇
  2013年   44篇
  2012年   46篇
  2011年   39篇
  2010年   19篇
  2009年   13篇
  2008年   22篇
  2007年   8篇
  2006年   6篇
  2005年   5篇
  2004年   2篇
  2003年   1篇
  2002年   1篇
  2001年   1篇
  1999年   1篇
  1983年   2篇
排序方式: 共有485条查询结果,搜索用时 218 毫秒
91.
92.
区域城镇风景特征与自然基底、历史进程、产业、人文等密切相关,梳理传统城镇风景要素及其空间分布、组织特征,对当代语境下的地域性城镇风景体系重构具有重要的指导与借鉴意义。川江流域城镇地处峡江地带,属典型的山地城镇,加之受悠久的演进历程和地域多元文化影响,其城镇风景极具历史及地方性特征。通过对方志、文集、诗歌等文字记载和相关图画资料进行量化统计、图文对照分析,梳理川江流域传统城镇风景要素数量、类型及位置分布;同时借助HGIS技术对城镇古代舆图、城图等进行地理信息的空间表达。归纳宏观视域下风景分布与山水构架的耦合关系,以及城镇及周边视域下城镇与风景互为补充和参照的融合关系。为构建多元的城镇风景要素、强化地方山水格局、促进城镇与风景协同发展等提供研究方法探究和理论指导  相似文献   
93.
94.
95.
In accordance with the structural characteristics of thiazolidinedione drugs and highly bioactive tyrosine derivatives, we tentatively designed the l-phenylglycine derivatives TM1 and TM2 based on basic principles of drug design and then synthesized them. The in vitro screening of peroxisome proliferator-activated receptor gamma (PPARγ) activated activity, α-glucosidase inhibitory and dipeptidyl peptidase-4 inhibitory activities showed that the novel molecule M5 had efficient PPAR response element (PPRE) activated activity (PPRE relative activity 105.04% at 10?μg·mL?1 compared with the positive control pioglitazone, with 100% activity). Therefore, M5 was selected as the hit compound from which the TM3 and TM4 series of compounds were further designed and synthesized. Based on the PPRE relative activities of TM3 and TM4, we discovered another new molecule, TM4h, which had the strongest PPRE relative activity (120.42% at 10?μg·mL?1). In addition, the concentration-dependent activity of the highly active compounds was determined by assaying their half-maximal effective concentration (EC50) values. The molecular physical parameter calculation and the molecular toxicity prediction were used to theoretically evaluate the lead-likeness and safety of the active compounds. In conclusion, we identified a potential PPARγ lead molecule and developed a tangible strategy for antidiabetic drug development.  相似文献   
96.
Sister‐chromatid cohesion mediated by the cohesin complex is fundamental for precise chromosome segregation in mitosis. Through binding the cohesin subunit Pds5, Wapl releases the bulk of cohesin from chromosome arms in prophase, whereas centromeric cohesin is protected from Wapl until anaphase onset. Strong centromere cohesion requires centromeric localization of the mitotic histone kinase Haspin, which is dependent on the interaction of its non‐catalytic N‐terminus with Pds5B. It remains unclear how Haspin fully blocks the Wapl–Pds5B interaction at centromeres. Here, we show that the C‐terminal kinase domain of Haspin (Haspin‐KD) binds and phosphorylates the YSR motif of Wapl (Wapl‐YSR), thereby directly inhibiting the YSR motif‐dependent interaction of Wapl with Pds5B. Cells expressing a Wapl‐binding‐deficient mutant of Haspin or treated with Haspin inhibitors show centromeric cohesion defects. Phospho‐mimetic mutation in Wapl‐YSR prevents Wapl from binding Pds5B and releasing cohesin. Forced targeting Haspin‐KD to centromeres partly bypasses the need for Haspin–Pds5B interaction in cohesion protection. Taken together, these results indicate a kinase‐dependent role for Haspin in antagonizing Wapl and protecting centromeric cohesion in mitosis.  相似文献   
97.
Temperature is an important environmental factor controlling plant growth, development, and immune response. However, the role of temperature in plant disease resistance is still elusive. In the present study, the potential effects of temperature on the interaction between Nicotiana tabacum and Cucumber mosaic virus (CMV) were investigated. Our results indicated that N. tabacum plants displayed severe symptoms at early stage of post inoculation at high temperature (HT, 28°C), associated with higher viral replication level, more serious stress damages. By contrast, low temperature (LT, 18°C) effectively delayed the replication of CMV compared with elevated temperatures. Additionally, quantitative real-time PCR analyses revealed that lower temperatures (≤ 24°C) promote salicylic acid (SA) dependent responses, whereas higher temperatures (> 24°C) activate the genes expression of jasmonic acid (JA) pathway. Interestingly, the dark green islands (DGIs) appeared much earlier in CMV-inoculated plants grown at HT compared with those at LT and the accumulation of virus small interfering RNAs in plants were significantly up-regulated under elevated temperatures at early stage of post inoculation. Taken together, these results indicated that temperature changes had important effects on plant defence response, and different temperatures could induce different immune pathways of N. tabacum against CMV infection.  相似文献   
98.
Cassava (Manihot esculenta Crantz) is a tropical root crop and sensitive to low temperature. However, it is poorly to know how cassava can modify its metabolism and growth to adapt to cold stress. An investigation aimed at a better understanding of cold-tolerant mechanism of cassava plantlets was carried out with the approaches of physiology and proteomics in the present study. The principal component analysis of seven physiological characteristics showed that electrolyte leakage (EL), chlorophyll content, and malondialdehyde (MDA) may be the most important physiological indexes for determining cold-resistant abilities of cassava. The genome-wide proteomic analysis showed that 20 differential proteins had the same patterns in the apical expanded leaves of cassava SC8 and Col1046. They were mainly related to photosynthesis, carbon metabolism and energy metabolism, defense, protein synthesis, amino acid metabolism, signal transduction, structure, detoxifying and antioxidant, chaperones, and DNA-binding proteins, in which 40 % were related with photosynthesis. The remarkable variation in photosynthetic activity and expression level of peroxiredoxin is closely linked with expression levels of proteomic profiles. Moreover, analysis of differentially expressed proteins under cold stress is an important step toward further elucidation of mechanisms of cold stress resistance.  相似文献   
99.
Genome‐wide association studies have successfully identified over 70 loci associated with the risk of type 2 diabetes mellitus (T2DM) in multiple populations of European ancestry. However, the risk attributable to an individual variant is modest and does not yet provide convincing evidence for clinical utility. Association between these established genetic variants and T2DM in general populations is hitherto understudied in the isolated populations, such as the Uyghurs, resident in Hetian, far southern Xinjiang Uyghur Autonomous Region, China. In this case–control study, we genotyped 13 single‐nucleotide polymorphisms (SNPs) at 10 genes associated with diabetes in 130 cases with T2DM and 135 healthy controls of Uyghur, a Chinese minority ethnic group. Three of the 13 SNPs demonstrated significant association with T2DM in the Uyghur population. There were significant differences between the T2DM patients and controls in the risk allele distributions of rs3792267 (CAPN10) (P = 0.002), rs1501299 (APM1) (P = 0.017), and rs3760776 (FUT6) (P = 0.031). Allelic carriers of rs3792267‐A, rs1501299‐T, and rs3760776‐T had a 2.24‐fold [OR (95% CI): 1.35–3.71], 0.59‐fold [OR (95% CI): 0.39–0.91], 0.57‐fold [OR (95% CI): 0.34–0.95] increased risk for T2DM respectively. We further confirmed that the cumulative risk allelic scores calculated from the 13 susceptibility loci for T2DM differed significantly between the T2DM patients and controls (P = 0.001), and the effect of obesity/overweight on T2DM was only observed in the subjects with a combined risk allelic score under a value of 17. This study observed that the SNPs rs3792267 in CAPN10, rs1501299 in APM1, and rs3760776 in FUT6 might serve as potential susceptible biomarkers for T2DM in Uyghurs. The cumulative risk allelic scores of multiple loci with modest individual effects are also significant risk factors in Uyghurs for T2DM, particularly among non‐obese individuals. This is the first investigation having observed/found genetic variations on genetic loci functionally linked with glycosylation associated with the risk of T2DM in a Uyghur population.  相似文献   
100.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号