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   233篇
  免费   26篇
  2022年   1篇
  2021年   3篇
  2020年   3篇
  2019年   5篇
  2018年   6篇
  2017年   4篇
  2016年   7篇
  2015年   5篇
  2014年   15篇
  2013年   11篇
  2012年   16篇
  2011年   12篇
  2010年   7篇
  2009年   6篇
  2008年   3篇
  2007年   11篇
  2006年   16篇
  2005年   10篇
  2004年   7篇
  2003年   11篇
  2002年   6篇
  2001年   7篇
  2000年   5篇
  1999年   6篇
  1998年   3篇
  1997年   4篇
  1996年   2篇
  1995年   2篇
  1994年   3篇
  1993年   6篇
  1992年   3篇
  1991年   9篇
  1990年   6篇
  1989年   5篇
  1988年   2篇
  1987年   7篇
  1986年   4篇
  1985年   4篇
  1984年   5篇
  1983年   1篇
  1982年   3篇
  1981年   2篇
  1978年   2篇
  1974年   1篇
  1973年   1篇
  1967年   1篇
排序方式: 共有259条查询结果,搜索用时 15 毫秒
201.
The distribution pattern of the Parmales, a recently described order of siliceous marine nanophytoplankton, is described and quantified in surface sediments of the Atlantic sector of the Southern Ocean. Additional samples were investigated from the Bransfield Strait and the eastern Bellingshausen Sea. Highest abundances occurred in nearshore areas of the southern and southeastern Weddell Sea. Due to the distribution of Parmales species, which is strictly linked to these neritic areas, influenced most of the year by sea ice, it is suggested that the presence of Parmales species may be an indicator of sea ice influence probably useful in later down core studies.  相似文献   
202.
The Karoo is a unique region in South Africa in terms of its ecological processes and endemic species. Large areas are needed to maintain viable populations of nomadic birds that follow erratic rainfall events and subsequent food and nesting resources, as well as ephemeral standing water. Whereas many species are adapted to arid conditions, our trait-based analysis found that an unusually large percentage (almost 45%) of 315 bird species in the semi-arid Karoo region rely on water to some degree. Indeed, some birds may have benefited from human activities to date, such as through the provision of water for livestock. However, this reliance on water makes birds vulnerable to changes in water quality stemming from various industrial developments. Given the large areas of the Karoo under consideration for concessions, the most noteworthy of these is hydraulic fracturing for shale gas, which results in a large quantity of waste water (‘produced water’) that contains a wide variety of chemicals, including petroleum byproducts. Given the negative impacts of secondary waste water on wildlife in other parts of the world where shale-gas exploration is being undertaken, careful attention must be given to preventing access to such produced water by an estimated 60 to 141 species of birds that make use of the water in the Karoo.  相似文献   
203.
204.
Brain insulin controls adipose tissue lipolysis and lipogenesis   总被引:1,自引:0,他引:1  
White adipose tissue (WAT) dysfunction plays a key role in the pathogenesis of type 2 diabetes (DM2). Unrestrained WAT lipolysis results in increased fatty acid release, leading to insulin resistance and lipotoxicity, while impaired de novo lipogenesis in WAT decreases the synthesis of insulin-sensitizing fatty acid species like palmitoleate. Here, we show that insulin infused into the mediobasal hypothalamus (MBH) of Sprague-Dawley rats increases WAT lipogenic protein expression, inactivates hormone-sensitive lipase (Hsl), and suppresses lipolysis. Conversely, mice that lack the neuronal insulin receptor exhibit unrestrained lipolysis and decreased de novo lipogenesis in WAT. Thus, brain and, in particular, hypothalamic insulin action play a pivotal role in WAT functionality.  相似文献   
205.
206.
One of the most important factors in choosing a treatment strategy for cancer is characterization of biomarkers in cancer cells. Particularly, recent advances in Monoclonal Antibodies (MAB) as primary-specific drugs targeting tumor receptors show that their efficacy depends strongly on characterization of tumor biomarkers. Assessment of their status in individual patients would facilitate selection of an optimal treatment strategy, and the continuous monitoring of those biomarkers and their binding process to the therapy would provide a means for early evaluation of the efficacy of therapeutic intervention. In this study we have demonstrated for the first time in live animals that the fluorescence lifetime can be used to detect the binding of targeted optical probes to the extracellular receptors on tumor cells in vivo. The rationale was that fluorescence lifetime of a specific probe is sensitive to local environment and/or affinity to other molecules. We attached Near-InfraRed (NIR) fluorescent probes to Human Epidermal Growth Factor 2 (HER2/neu)-specific Affibody molecules and used our time-resolved optical system to compare the fluorescence lifetime of the optical probes that were bound and unbound to tumor cells in live mice. Our results show that the fluorescence lifetime changes in our model system delineate HER2 receptor bound from the unbound probe in vivo. Thus, this method is useful as a specific marker of the receptor binding process, which can open a new paradigm in the "image and treat" concept, especially for early evaluation of the efficacy of the therapy.  相似文献   
207.
Chemical sensory signals play a crucial role in eliciting motor behaviors. We now review the different motor behaviors induced by chemosensory stimuli in fish as well as their neural substrate. A great deal of research has focused on migratory, reproductive, foraging, and escape behaviors but it is only recently that the molecules mediating these chemotactic responses have become well-characterized. Chemotactic responses are mediated by three sensory systems: olfactory, gustatory, and diffuse chemosensory. The olfactory sensory neuron responses to chemicals are now better understood. In addition, the olfactory projections to the central nervous system were recently shown to display an odotopic organization in the forebrain. Moreover, a specific downward projection underlying motor responses to olfactory inputs was recently described.  相似文献   
208.
We constructed pIGPZ, a new cloning and expression vector derived from Escherichia coli plasmid pIGWZ12::Kan. pIGPZ contains a kanamycin resistance marker, a multiple-cloning-site (MCS) region, and a promoter for constitutive expression of cloned genes. pIGPZ has the same high level of stability as the original plasmid, even in the absence of antibiotic selection. Furthermore, we show that pIGPZ is compatible with ColE1-based plasmids and a pSC101-like plasmid. All the characteristic elements of theta-replicating plasmids were found in the pIGPZ putative origin of replication. Finally, we demonstrate that pIGPZ can be used in a double-plasmid expression system by co-expressing UBP1 protease from pIGPZ with ubi-interferon alpha (IFNA13; GenBank Accession No. NM_006900.3) or ubi-human growth hormone (ubi-hGH; patent No. WO 2005/066208 A2) cloned in another plasmid. In this system, both ubi-interferon alpha and ubi-human growth hormone were deubiquitinated efficiently in E. coli cells.  相似文献   
209.
Human epidermal growth factor receptor type 2 (HER2) is a well-known biomarker that is overexpressed in many breast carcinomas. HER2 expression level is an important factor to optimize the therapeutic strategy and monitor the treatment. We used albumin binding domain-fused HER2-specific Affibody molecules, labeled with Alexa Fluor750 dye, to characterize HER2 expression in vivo. Near-infrared optical imaging studies were carried out using mice with subcutaneous HER2-positive tumors. Animals were divided into groups of five: no treatment and 12 hours and 1 week after treatment of the tumors with the Hsp90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG). The compartmental ligands-receptor model, describing binding kinetics, was used to evaluate HER2 expression from the time sequence of the fluorescence images after the intravenous probe injection. The normalized rate of accumulation of the specific fluorescent biomarkers, estimated from this time sequence, linearly correlates with the conventional ex vivo enzyme-linked immunosorbent assay (ELISA) readings for the same tumor. Such correspondence makes properly arranged fluorescence imaging an excellent candidate for estimating HER2 overexpression in tumors, complementing ELISA and other ex vivo assays. Application of this method to the fluorescence data from HER2-positive xenografts reveals that the 17-DMAG treatment results in downregulation of HER2. Application of the AngioSense 750 probe confirmed the antiangiogenic effect of 17-DMAG found with Affibody-Alexa Fluor 750 conjugate.  相似文献   
210.
With high productivity and stress tolerance, numerous grass genera of the Andropogoneae have emerged as candidates for bioenergy production. To optimize these candidates, research examining the genetic architecture of yield, carbon partitioning, and composition is required to advance breeding objectives. Significant progress has been made developing genetic and genomic resources for Andropogoneae, and advances in comparative and computational genomics have enabled research examining the genetic basis of photosynthesis, carbon partitioning, composition, and sink strength. To provide a pivotal resource aimed at developing a comparative understanding of key bioenergy traits in the Andropogoneae, we have established and characterized an association panel of 390 racially, geographically, and phenotypically diverse Sorghum bicolor accessions with 232,303 genetic markers. Sorghum bicolor was selected because of its genomic simplicity, phenotypic diversity, significant genomic tools, and its agricultural productivity and resilience. We have demonstrated the value of sorghum as a functional model for candidate gene discovery for bioenergy Andropogoneae by performing genome-wide association analysis for two contrasting phenotypes representing key components of structural and non-structural carbohydrates. We identified potential genes, including a cellulase enzyme and a vacuolar transporter, associated with increased non-structural carbohydrates that could lead to bioenergy sorghum improvement. Although our analysis identified genes with potentially clear functions, other candidates did not have assigned functions, suggesting novel molecular mechanisms for carbon partitioning traits. These results, combined with our characterization of phenotypic and genetic diversity and the public accessibility of each accession and genomic data, demonstrate the value of this resource and provide a foundation for future improvement of sorghum and related grasses for bioenergy production.  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