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   3064篇
  免费   200篇
  国内免费   139篇
  2024年   6篇
  2023年   56篇
  2022年   129篇
  2021年   247篇
  2020年   171篇
  2019年   212篇
  2018年   193篇
  2017年   134篇
  2016年   199篇
  2015年   255篇
  2014年   336篇
  2013年   330篇
  2012年   314篇
  2011年   278篇
  2010年   138篇
  2009年   107篇
  2008年   103篇
  2007年   77篇
  2006年   43篇
  2005年   34篇
  2004年   21篇
  2003年   10篇
  2002年   6篇
  2001年   1篇
  2000年   1篇
  1959年   2篇
排序方式: 共有3403条查询结果,搜索用时 15 毫秒
991.
992.
The present study proposed a deep learning (DL) algorithm to predict survival in patients with colon adenocarcinoma (COAD) based on multiomics integration. The survival-sensitive model was constructed using an autoencoder for DL implementation based on The Cancer Genome Atlas (TCGA) data of patients with COAD. The autoencoder framework was compared with PCA, NMF, t-SNE, and univariable Cox-PH model for identifying survival-related features. The prognostic robustness of the inferred survival risk groups was validated using three independent confirmation cohorts. Differential expression analysis, Pearson’s correlation analysis, construction of miRNA–target gene network, and function enrichment analysis were performed. Two risk groups with significant survival differences were identified in TCGA set using the autoencoder-based model (log-rank P-value = 5.51e−07). The autoencoder framework showed superior performance compared with PCA, NMF, t-SNE, and the univariable Cox-PH model based on the C-index, log-rank P-value, and Brier score. The robustness of the classification model was successfully verified in three independent validation sets. There were 1271 differentially expressed genes, 10 differentially expressed miRNAs, and 12 hypermethylated genes between the survival risk groups. Among these, miR-133b and its target genes (GNB4, PTPRZ1, RUNX1T1, EPHA7, GPM6A, BICC1, and ADAMTS5) were used to construct a network. These genes were significantly enriched in ECM–receptor interaction, focal adhesion, PI3K–Akt signaling pathway, and glucose metabolism-related pathways. The risk subgroups obtained through a multiomics data integration pipeline using the DL algorithm had good robustness. miR-133b and its target genes could be potential diagnostic markers. The results would assist in elucidating the possible pathogenesis of COAD.  相似文献   
993.
ABSTRACT

Many phenolic compounds, derived from lignin during the pretreatment of lignocellulosic biomass, could obviously inhibit the activity of cellulolytic and hemicellulolytic enzymes. Acetosyringone (AS) is one of the phenolic compounds produced from lignin degradation. In this study, we investigated the inhibitory effects of AS on xylanase activity through kinetic experiments. The results showed that AS could obviously inhibit the activity of xylanase in a reversible and noncompetitive binding manner (up to 50% activity loss). Inhibitory kinetics and constants of xylanase on AS were conducted by the HCH-1 model (β = 0.0090 ± 0.0009 mM?1). Furthermore, intrinsic and 8-anilino-1-naphthalenesulfonic (ANS)-binding fluorescence results showed that the tertiary structure of AS-mediated xylanase was altered. These findings provide new insights into the role of AS in xylanase activity. Our results also suggest that AS was an inhibitor of xylanase and targeting AS was a potential strategy to increase xylose production.  相似文献   
994.
ABSTRACT

Allicin is a natural product suppressing the progression of gastric carcinoma (GC). In the current study, the mechanism underlying the anti-GC effect of allicin was explored by focusing on the role of miR-383-5p/ERBB4 signaling. Two GC cell lines were treated with allicin and the effects on viability, apoptosis, migration, invasion, and miR-383-5p/ERBB4 activity in the cells were assessed. The interaction between allicin and miR-383-5p was further explored by inhibiting the miR-383-5p level. Allicin suppressed cell viability and induced apoptosis in both GC cell lines. The compound also inhibited migration and invasion of GC cells, which was associated with the up-regulation miR-383-5p and down-regulation of ERBB4. The inhibition of miR-383-5p by specific inhibitor blocked the anti-GC effect of allicin. Our results demonstrated that allicin contributed to the suppressed growth and metastasis potentials in GC cell lines. The effect was accompanied by an increased level of miR-383-5p and subsequent inhibition of ERBB4.  相似文献   
995.
黄酮类化合物是一类重要的次生代谢产物,广泛存在于各种植物和真菌中,具有抗菌、抗癌、抗氧化等生物活性。本研究以提取毛木耳子实体中总黄酮量为考察指标,运用响应面分析法研究了超声功率、浸提时间、乙醇浓度和料液比4个因素对总黄酮提取量的影响,以获得提取毛木耳总黄酮的最优工艺。经响应面分析,各因素按照对响应值的影响顺序为:浸提时间>超声功率>乙醇浓度>料液比,且超声功率、浸提时间、乙醇浓度对总黄酮提取量的影响极显著。结果表明提取毛木耳子实体中总黄酮含量的最优工艺为:超声功率168W、浸提时间50min、乙醇浓度60%、料液比1:7,总黄酮的最大预测提取量为2.11%。验证试验结果表明,总黄酮含量平均为2.08%,与理论值基本吻合。本研究将为食用菌中总黄酮的提取工艺提供理论基础。  相似文献   
996.
随着我国印染工业的发展,废水对生态环境的危害日趋严重,亟需开发一种脱色明显且成本低廉的降解方法。本研究发现毛木耳Auricularia cornea菌株AC5对不同结构的染料均具有一定的降解作用,尤其是三苯甲烷类染料。利用26℃、160r/min振荡培养7d的粗酶液对染料(75.0mg/L)进行12h降解,结果显示三苯甲烷染料孔雀石绿、结晶紫,蒽醌染料活性蓝19和偶氮染料活性蓝222的降解效率分别为83.27%、71.77%、67.81%和63.92%。染料降解实验和酶活力测定结果表明,毛木耳对孔雀石绿的降解率达到最高时漆酶活性最高,为321.0U/mL,木质素过氧化物酶和锰过氧化物酶活性较低。因此,推测在降解过程中漆酶起到主要作用。研究表明利用毛木耳菌丝发酵液降解染料废水成本低且操作方便,为染料废水的降解研究提供了前期基础。  相似文献   
997.
998.
Increasing human health and longevity is of global interest. Environmental, genetic, and stochastic factors all affect longevity. Among these factors, the environment is extremely important. To investigate the relationship between the environment and longevity, we studied the environment in Zhongxiang (China), where the inhabitants commonly have long life spans. Air was analyzed for negative oxygen ions, SO2, and inhalable particles, while drinking water and rice were analyzed for macro- and micro-elements. The air quality in this area was determined to be grade I with high negative oxygen ion content and low SO2 and inhalable particle contents. Apart from Fe, Mn, and F, all tested elements and the pH were within national standards and World Health Organization guidelines. The percentage of long-lived people in the area was closely related to the macro- and micro-element contents of their staple food, rice. The elements in rice could be classified into three categories according to their effect on longevity: Sr, Ca, Al, Mo, and Se, which were positively correlated with longevity; Fe, Mn, Zn, Cr, P, Mg, and K, which had a weak effect on local longevity, and Cu and Ba, which had a negative effect on longevity.  相似文献   
999.
Liu B  Wu Q  Lv D  Lin X 《Journal of biotechnology》2011,153(3-4):111-115
This paper reported the modulation of enzyme activity by organic small molecule. The esterification activity of Penicillin G acylase (PGA) was improved more than 70-fold by the addition of 10% N-methylimidazole. Some control experiments have been designed to demonstrate the catalytic specificity of PGA. The structure and the amount of additive were optimized to improve the product yield. The influence of N-methylimidazole on the PGA conformation was investigated by FTIR and autodock simulation. Seven substrates were used to evaluate the effect of structure on the PGA-catalyzed transesterification. A series of products were successfully synthesized with the yield ranged from 56% to 84% and PGA showed specific recognition on the substrate with phenyl group in the presence of 10% N-methylimidazole.  相似文献   
1000.
-Di(2-ethylhexyl) phthalate (DEHP), a typical endocrine-disrupting chemical (EDC), is widely used as plasticizer. DEHP exposure in humans is virtually ubiquitous, and those undergoing certain medical procedures can be especially high. In this study, we investigated whether developmental DEHP exposure disrupted glucose homeostasis in the rat and whether this was associated with the early impairment in endocrine pancreas. Pregnant Wistar rats were administered DEHP (1.25 and 6.25 mg·kg(-1)·day(-1)) or corn oil throughout gestation and lactation by oral gavage. Body weight, glucose and insulin tolerance, and β-cell morphometry and function were examined in offspring during the growth. In this study, developmental DEHP exposure led to abnormal β-cell ultrastructure, reduced β-cell mass, and pancreatic insulin content as well as alterations in the expression of genes involved in pancreas development and β-cell function in offspring at weaning. At adulthood, female DEHP-exposed offspring exhibited elevated blood glucose, reduced serum insulin, impaired glucose tolerance, and insulin secretion. Male DEHP-exposed offspring had increased serum insulin, although there were no significant differences in blood glucose at fasting and during glucose tolerance test. In addition, both male and female DEHP-exposed offspring had significantly lower birth weight and maintained relatively lower body weight up to 27 wk of age. These results suggest that developmental exposure to DEHP gives rise to β-cell dysfunction and the whole body glucometabolic abnormalities in the rat. DEHP exposure in critical periods of development can be a potential risk factor, at least in part, for developing diabetes.  相似文献   
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