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   216篇
  免费   18篇
  2023年   1篇
  2022年   3篇
  2021年   4篇
  2020年   1篇
  2019年   3篇
  2018年   10篇
  2017年   7篇
  2016年   10篇
  2015年   14篇
  2014年   20篇
  2013年   16篇
  2012年   24篇
  2011年   18篇
  2010年   13篇
  2009年   8篇
  2008年   8篇
  2007年   10篇
  2006年   7篇
  2005年   6篇
  2004年   9篇
  2003年   8篇
  2002年   7篇
  2001年   3篇
  2000年   4篇
  1999年   2篇
  1998年   2篇
  1997年   1篇
  1996年   3篇
  1994年   3篇
  1991年   1篇
  1990年   1篇
  1987年   2篇
  1980年   1篇
  1979年   1篇
  1978年   2篇
  1976年   1篇
排序方式: 共有234条查询结果,搜索用时 15 毫秒
81.
82.
Pancreatic ductal adenocarcinomas contain a subset of exclusively tumorigenic cancer stem cells (CSCs), which are capable of repopulating the entire heterogeneous cancer cell populations and are highly resistant to standard chemotherapy. Here we demonstrate that metformin selectively ablated pancreatic CSCs as evidenced by diminished expression of pluripotency-associated genes and CSC-associated surface markers. Subsequently, the ability of metformin-treated CSCs to clonally expand in vitro was irreversibly abrogated by inducing apoptosis. In contrast, non-CSCs preferentially responded by cell cycle arrest, but were not eliminated by metformin treatment. Mechanistically, metformin increased reactive oxygen species production in CSC and reduced their mitochondrial transmembrane potential. The subsequent induction of lethal energy crisis in CSCs was independent of AMPK/mTOR. Finally, in primary cancer tissue xenograft models metformin effectively reduced tumor burden and prevented disease progression; if combined with a stroma-targeting smoothened inhibitor for enhanced tissue penetration, while gemcitabine actually appeared dispensable.  相似文献   
83.
84.
85.
Molecular Biology Reports - In adulthood the activity of the lactase enzyme is inherited as autosomal dominant form associated to Single nucleotide polymorphisms (SNPs). The present research was...  相似文献   
86.
Iron and palladium binding an exopolysaccharide (EPS) were obtained and purified from cultures of bacterial cells of Klebsiella oxytoca BAS-10. The strain BAS-10 was able to grow under anaerobic conditions with Fe(III)-citrate as energy and carbon source, producing Fe(III)-EPS that was extracted and used as catalyst in the oxidation reaction of phenol with H(2)O(2). The same bacterial strain was cultivated anaerobically with Na-citrate and Pd(2)(NO)(3) was added during the exponential growth to afford a Pd-EPS, named Bio-Pd (A), that, after isolation and purification, was used as catalyst in the reductive dehalogenation of chlorobenzene as model reaction. For comparison other two palladium binding polysaccharides were prepared: (a) a second type Pd-EPS, named Bio-Pd (B), was obtained by an exchange reaction with Pd acetate starting from an iron-free EPS produced by strain BAS-10 growing on Na-citrate medium; (b) a third type of palladium, named Bio-Pd (C), bound to a different polysaccharide, was recovered after the same exchange reaction applied on glycolipid emulsan obtained from an aerobic culture of Acinetobacter venetianus RAG 1. The superiority of Bio-Pd (A), as catalyst, vs Bio-Pd (B) and (C) was demonstrated. This approach to use microorganisms to prepare metal bound polysaccharides is novel and permits to prepare metal species, sequestrated in aqueous phase that can be useful either as catalysts for synthetic applications or to support the microbial biotransformation of pollutants.  相似文献   
87.
88.
Highlights? Latent enhancers are regulatory elements unmarked and unbound in differentiated cells ? Stimulus-dependent TFs co-opt lineage-determining TFs to activate latent enhancers ? Latent enhancers may confer short-term memory of environmental exposure ? Environmental stimulation qualitatively alters the pre-existing enhancer repertoire  相似文献   
89.
MODY2 is the most prevalent monogenic form of diabetes in Italy with an estimated prevalence of about 0.5–1.5%. MODY2 is potentially indistinguishable from other forms of diabetes, however, its identification impacts on patients'' quality of life and healthcare resources. Unfortunately, DNA direct sequencing as diagnostic test is not readily accessible and expensive. In addition current guidelines, aiming to establish when the test should be performed, proved a poor detection rate. Aim of this study is to propose a reliable and easy-to-use tool to identify candidate patients for MODY2 genetic testing. We designed and validated a diagnostic flowchart in the attempt to improve the detection rate and to increase the number of properly requested tests. The flowchart, called 7-iF, consists of 7 binary “yes or no” questions and its unequivocal output is an indication for whether testing or not. We tested the 7-iF to estimate its clinical utility in comparison to the clinical suspicion alone. The 7-iF, in a prospective 2-year study (921 diabetic children) showed a precision of about the 76%. Using retrospective data, the 7-iF showed a precision in identifying MODY2 patients of about 80% compared to the 40% of the clinical suspicion. On the other hand, despite a relatively high number of missing MODY2 patients, the 7-iF would not suggest the test for 90% of the non-MODY2 patients, demonstrating that a wide application of this method might 1) help less experienced clinicians in suspecting MODY2 patients and 2) reducing the number of unnecessary tests. With the 7-iF, a clinician can feel confident of identifying a potential case of MODY2 and suggest the molecular test without fear of wasting time and money. A Qaly-type analysis estimated an increase in the patients'' quality of life and savings for the health care system of about 9 million euros per year.  相似文献   
90.
Ecoacoustic techniques using multiple acoustic sensors and two metrics of the acoustic community – the acoustic complexity index (ACI) and the chorus ratio (CR) – were successfully used to describe and characterize the morning acoustic activity of birds according to three equal temporal intervals during spring 2013: Dawn Chorus, Post Chorus 1, and Post Chorus 2.The metrics were applied across five Italian Mediterranean locations (Valenza, Madonna dei Colli, Monte Curto, Virolo, Croce di Tergagliana) that differed by land-cover typologies. Results from the ACI metrics showed a peak during the Dawn Chorus and a visible lull close to sunrise between Dawn Chorus and Post Chorus 1.The lull was evident in all localities except Valenza, where singing activity was relatively constant across the successive morning intervals. Temperature and vegetation structure were confirmed as important factors associated with morning acoustic activities. Vegetation evenness and temperature across the season was negatively correlated with ACI, whereas CR was positively correlated with temperature and vegetation diversity. Of the 33 species of birds identified during the maximum dawn chorus activity, Blackcap, Blackbird, European Robin, and Great Tit were acoustically dominant and their activity was significantly higher before sunrise except for Blackcap, whose acoustic activity showed no significant differences across time intervals. The dawn chorus is one of the most conspicuous behaviours of birds, engendering much speculation but no definitive, univocal explanations. The ecoacoustic approach opens a new perspective for investigating this complex phenomenon.  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