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   301篇
  免费   12篇
  313篇
  2024年   2篇
  2023年   1篇
  2022年   2篇
  2021年   12篇
  2020年   6篇
  2019年   5篇
  2018年   7篇
  2017年   5篇
  2016年   9篇
  2015年   12篇
  2014年   16篇
  2013年   16篇
  2012年   26篇
  2011年   19篇
  2010年   21篇
  2009年   13篇
  2008年   23篇
  2007年   16篇
  2006年   18篇
  2005年   4篇
  2004年   17篇
  2003年   10篇
  2002年   8篇
  2001年   5篇
  2000年   1篇
  1999年   1篇
  1998年   1篇
  1996年   3篇
  1995年   4篇
  1994年   5篇
  1992年   5篇
  1991年   2篇
  1990年   1篇
  1989年   1篇
  1988年   2篇
  1982年   2篇
  1979年   1篇
  1978年   1篇
  1977年   1篇
  1974年   1篇
  1968年   1篇
  1967年   1篇
  1966年   2篇
  1965年   1篇
  1964年   1篇
  1962年   1篇
  1961年   1篇
排序方式: 共有313条查询结果,搜索用时 15 毫秒
71.
We report the case of a 63-year-old man, investigated for staging of a prostatic cancer, diagnosed by biopsy, following a rise in the prostatic specific antigen (PSA) on a systematic assessment. The interrogation before examination revealed signs of beginning right crural neuropathy. The hydroxymethylene diphosphonate technetium 99m-labeled (99mTc-HDP) whole-body bone scintigraphy highlighted two extraosseous uptake images, the first of moderated intensity in the right iliac area, the second milder, in the abdominal median area. Osseous metastases were not visualized. The single photon emission computerized tomography guided by computerized tomography (SPECT/CT) identified the median abdominal mass which corresponded to a bulky aneurysm of the under renal abdominal aorta. The right iliac mass could be accurately analyzed and differentiated from the various organs of the abdominopelvic cavity. Its lymphatic origin was hypothetised, but the diagnosis of lymphatic metastasis of the prostatic cancer was obtained by the pathologic examination of CT scan-guided biopsy.  相似文献   
72.
In addition to its classical CD40 receptor, CD154 also binds to αIIbβ3, α5β1, and αMβ2 integrins. Binding of CD154 to these receptors seems to play a key role in the pathogenic processes of chronic inflammation. This investigation was aimed at analyzing the functional interaction of CD154 with CD40, αIIbβ3, and α5β1 receptors. We found that the binding affinity of CD154 for αIIbβ3 is ~4-fold higher than for α5β1. We also describe the generation of sCD154 mutants that lost their ability to bind CD40 or αIIbβ3 and show that CD154 residues involved in its binding to CD40 or αIIbβ3 are distinct from those implicated in its interaction to α5β1, suggesting that sCD154 may bind simultaneously to different receptors. Indeed, sCD154 can bind simultaneously to CD40 and α5β1 and biologically activate human monocytic U937 cells expressing both receptors. The simultaneous engagement of CD40 and α5β1 activates the mitogen-activated protein kinases, p38, and extracellular signal-related kinases 1/2 and synergizes in the release of inflammatory mediators MMP-2 and -9, suggesting a cross-talk between these receptors.  相似文献   
73.
Goal, Scope and Background  Despite the well-known advantages of recycling materials to reduce solid waste or save natural resources, the recycling stage is an additional process within the life cycle that has its own energy and input requirements, as well as specific emissions. The objective of the present paper is to analyze the life cycle inventory associated with the increase in recycling rate (from 2% up to 22% at present) of the cardboard contained in the aseptic packaging for long-life milk. The main aspects of the manufacturing of the Tetra Pak aseptic package, including the filling of the product, the distribution of the conditioned product, up to the final disposal and recycling rates, were considered. Materials and Methods  This study was conducted in accordance with the general directives of the ISO 14040 series. The packaging material system was assessed using 1000 liters of milk as a functional unit, in a packaging system containing 12 units of 1 L cartons each, placed on a corrugated paperboard tray wrapped in polyethylene shrink film and arranged onto one-way wooden pallets. Brazilian inventories for energy, carton, corrugated paperboard and aluminum, based on site-collected data were employed. The final disposal of used packages was modeled using the Average Brazilian Municipal Solid Waste Management data collected for the purpose of the census of the year 2000. Results  Comparison of the total energy consumption throughout the whole life cycle of two recycling scenarios (i.e. different recycling rates) analyzed shows that the higher recycling rate led to a 6% reduction of the total energy requirement for the long-life milk package material system. The most significant reductions in the consumption of natural resources were: 8% water, 11% wood and 10% land use savings. Greenhouse gases were the main reduced air emissions and contributed with a reduction of 9.7% in GWP. Most water emissions were reduced: 10% COD, 9% BOD and 6% TSS. A unique drawback directly caused by the increase of the recycling rate was an increase of 14.4 g in TDS emissions (57%). Discussion  The reduction in energy requirements are related and limited to the proportionality among the different materials that make up the packaging system. Most emission reductions result from the replacement of virgin materials with recycled materials in the packaging system. Although the average balance of water emissions is positive, the need to improve wastewater treatment processes in the paper recycling plants to reduce TDS is highlighted as a key issue. Conclusions  It may be concluded that the increase in the recycling rate brings about a series of benefits in terms of reduction of energy and natural resource consumption, air pollutants and most water emissions. In this case, the increase of the recycling rate improved the overall environmental performance of the aseptic Tetra Pak system for milk. Recommendations and Perspectives  The authors are currently analyzing alternative recycling scenarios that will enable one to evaluate maximum reduction in GWP. Further studies could include the agriculture stages, livestock and consumer phase to broaden the environmental evaluation. ESS-Submission Editor: Dr. Andreas A. Detzel (andreas.detzel@ifeu.de)  相似文献   
74.
Glucose-induced insulin secretion (IS) by β-cells is controlled by two pathways. The triggering pathway involves ATP-sensitive potassium (K(ATP)) channel-dependent depolarization, Ca(2+) influx, and rise in the cytosolic Ca(2+) concentration ([Ca(2+)](c)), which triggers exocytosis of insulin granules. The metabolic amplifying pathway augments IS without further increasing [Ca(2+)](c). After exclusion of the contribution of actin microfilaments, we here tested whether amplification implicates microtubule-dependent granule mobilization. Mouse islets were treated with nocodazole or taxol, which completely depolymerized and polymerized tubulin. They were then perifused to measure [Ca(2+)](c) and IS. Metabolic amplification was studied during imposed steady elevation of [Ca(2+)](c) by tolbutamide or KCl or by comparing [Ca(2+)](c) and IS responses to glucose and tolbutamide. Nocodazole did not alter [Ca(2+)](c) or IS changes induced by the three secretagogues, whereas taxol caused a small inhibition of IS that is partly ascribed to a decrease in [Ca(2+)](c). When [Ca(2+)](c) was elevated and controlled by KCl or tolbutamide, the amplifying action of glucose was unaffected by microtubule disruption or stabilization. Both phases of IS were larger in response to glucose than tolbutamide, although triggering [Ca(2+)](c) was lower. This difference, due to amplification, persisted in nocodazole- or taxol-treated islets, even when IS was augmented fourfold by microfilament disruption with cytochalasin B or latrunculin B. In conclusion, metabolic amplification rapidly augments first and second phases of IS independently of insulin granule translocation along microtubules. We therefore extend our previous proposal that it does not implicate the cytoskeleton but corresponds to acceleration of the priming process conferring release competence to insulin granules.  相似文献   
75.
LeIF, a Leishmania protein similar to the eukaryotic initiation factor eIF4A, which is a prototype of the DEAD box protein family, was originally described as a Th1-type natural adjuvant and as an antigen that induces an IL12-mediated Th1 response in the peripheral blood mononuclear cells of leishmaniasis patients. This study aims to characterize this protein by comparative biochemical and genetic analysis with eIF4A in order to assess its potential as a target for drug development. We show that a His-tagged, recombinant, LeIF protein of Leishmania infantum, which was purified from Escherichia coli, is both an RNA-dependent ATPase and an ATP-dependent RNA helicase in vitro, as described previously for other members of the DEAD box helicase protein family. In vivo experiments show that the LeIF gene cannot complement the deletion of the essential TIF1 and TIF2 genes in the yeast Saccharomyces cerevisiae that encode eIF4A. In contrast, expression of LeIF inhibits yeast growth when endogenous eIF4A is expressed off only one of its two encoding genes. Furthermore, in vitro binding assays show that LeIF interacts with yeast eIF4G. These results show an unproductive interaction of LeIF with translation initiation factors in yeast. Furthermore, the 25 amino terminal residues were shown to enhance the ability of LeIF to interfere with the translation machinery in yeast.  相似文献   
76.
Field and laboratory experiments were conducted in March, 2008 in El-Nouzha garden, Alexandria governorate. Pre-and post treatment inspections of the insects were examined and recorded before and after (2,4,8, and 12 weeks). Spraying was applied to evaluate the efficiency of the tested compounds, [Mineral oils (KZ oil and Star oil); IGRs (Chlorfluazuron, lufenuron and pyriproxyfen); Neem oil; emamectin benzoate and thiamethoxam]. Percentages of reduction were calculated. The ensign scale insects Insignorthezia insignis (Browne) were collected from treated Lantana camara shrubs to investigate the effect of the tested chemicals on Aspartate transferase (AST), Alanine transferase (ALT) and Alkaline-phosphatase (ALPK) of the insect enzymes activities. From the obtained results, it could be concluded that the tested materials gave good results for controlling both adult and immature stages of the ensign scale insect Insignorthezia insignis (Browne) that infested Lantana camara shrubs, through affecting enzymes activities of the assigned insect pest.  相似文献   
77.
The restoration of endangered relict populations is challenging in conservation biology because they require specific environmental conditions within an inhospitable regional climate. Urothemis edwardsii Selys is the most endangered dragonfly in the Mediterranean with only one known relict small population (Lac Bleu) left in Northeast Algeria. With the absence of successful (re-)colonization over the last two decades, the restoration of the species became a top priority. To improve the status of the species in Northeast Algeria, we carried out a reintroduction and translocation scheme during 2011–2015 and assessed the changes in distribution and population size. Our restoration plan led to the emergence of three populations of which one was restored (Lac Noir), one resulted from successful translocation (Lac Tonga Northeast), and one established after successful colonization (Lac Tonga Southwest). In three localities (Lac Noir, Lac Tonga Northeast, and Lac Tonga Southwest), signs of population growth were observed, whereas no significant trend in the source population (Lac Bleu) was detected. A new population (El Graeate) was also recorded in 2015, but its origin is uncertain. Capture-mark-recapture on adults conducted in 2015 in two sites (Lac Bleu and Lac Noir) showed low recapture rates and no sign of dispersal between the two sites. Dispersal capacity of the species and conservation implications of adult distribution are discussed. This study highlights the importance of using biological indicators in selecting host habitats for the restoration of critically threatened populations.  相似文献   
78.
The beta 1,6 N-acetylglucosaminyltransferase (C2GnT) has been recently mapped to the cis/medial-Golgi compartment. To analyze the Golgi-targeting determinants of C2GnT, we constructed various deletion mutants of the enzyme fused to the enhanced green fluorescent protein (EGFP) and localized these proteins by fluorescence microscopy in living cells. We found that the N-terminal peptide encompassing amino acids 1 to 32 represents the minimal Golgi-targeting signal sufficient to localize EGFP to the same compartment as the full-length C2GnT. This peptide makes up the cytoplasmic and the transmembrane domains of the enzyme and was referred to as CTd (cytoplasmic and transmembrane domains). We compared the Golgi-targeting efficiency of the C2GnT-derived CTd with its homologous domains from other glycosyltransferases, including the H-type alpha(1,2)-fucosyltransferase (FucTI), the polypeptide N-acetylgalactosaminyltransferase-I (GalNAcT-I), the alpha(1,3)-fucosyltransferase VII (FucTVII), and the alpha(2,6)-sialyltransferase (ST6Gal-I) and found that the Golgi-targeting determinants of these glycosyltransferases were also composed of their cytosolic and transmembrane domains. To investigate whether the CTd of C2GnT could serve as a cis to medial Golgi-specific signal, we tested its ability to mislocalize two late-Golgi acting glycosyltransferases FucTI and FucTVII. We show that fusing the C2GnT-derived CTd with the catalytic domain of FucTVII resulted in a complete mislocalization of the enzyme to the C2GnT compartment, with a parallel alteration of sialyl-Lewis x synthesis and P-selectin binding. The intracellular distribution and activity of FucTI, however, were not affected. Thus, CTds of either early or late-Golgi acting glycosyltransferases represent the Golgi-targeting domains of these enzymes. In addition, we show that C2GnT-derived CTd can function as a cis/medial Golgi-targeting determinant.  相似文献   
79.
The endosomal compartment of hepatic parenchymal cells contains an acidic endopeptidase, endosomal acidic insulinase, which hydrolyzes internalized insulin and generates the major primary end product A(1--21)-B(1--24) insulin resulting from a major cleavage at residues Phe(B24)-Phe(B25). This study addresses the nature of the relevant endopeptidase activity in rat liver that is responsible for most receptor-mediated insulin degradation in vivo. The endosomal activity was shown to be aspartic acid protease cathepsin D (CD), based on biochemical similarities to purified CD in 1) the rate and site of substrate cleavage, 2) pH optimum, 3) sensitivity to pepstatin A, and 4) binding to pepstatin A-agarose. The identity of the protease was immunologically confirmed by removal of greater than 90% of the insulin-degrading activity associated with an endosomal lysate using polyclonal antibodies to CD. Moreover, the elution profile of the endosomal acidic insulinase activity on a gel-filtration TSK-GEL G3000 SW(XL) high performance liquid chromatography column corresponded exactly with the elution profile of the immunoreactive 45-kDa mature form of endosomal CD. Using nondenaturating immunoprecipitation and immunoblotting procedures, other endosomal aspartic acid proteases such as cathepsin E and beta-site amyloid precursor protein-cleaving enzyme (BACE) were ruled out as candidate enzymes for the endosomal degradation of internalized insulin. Immunofluorescence studies showed a largely vesicular staining pattern for internalized insulin in rat hepatocytes that colocalized partially with CD. In vivo pepstatin A treatment was without any observable effect on the insulin receptor content of endosomes but augmented the phosphotyrosine content of the endosomal insulin receptor after insulin injection. These results suggest that CD is the endosomal acidic insulinase activity which catalyzes the rate-limiting step of the in vivo cleavage at the Phe(B24)-Phe(B25) bond, generating the inactive A(1--21)-B(1--24) insulin intermediate.  相似文献   
80.
The advent of high-throughput phenotyping technologies has created a deluge of information that is difficult to deal with without the appropriate data management tools. These data management tools should integrate defined workflow controls for genomic-scale data acquisition and validation, data storage and retrieval, and data analysis, indexed around the genomic information of the organism of interest. To maximize the impact of these large datasets, it is critical that they are rapidly disseminated to the broader research community, allowing open access for data mining and discovery. We describe here a system that incorporates such functionalities developed around the Purdue University high-throughput ionomics phenotyping platform. The Purdue Ionomics Information Management System (PiiMS) provides integrated workflow control, data storage, and analysis to facilitate high-throughput data acquisition, along with integrated tools for data search, retrieval, and visualization for hypothesis development. PiiMS is deployed as a World Wide Web-enabled system, allowing for integration of distributed workflow processes and open access to raw data for analysis by numerous laboratories. PiiMS currently contains data on shoot concentrations of P, Ca, K, Mg, Cu, Fe, Zn, Mn, Co, Ni, B, Se, Mo, Na, As, and Cd in over 60,000 shoot tissue samples of Arabidopsis (Arabidopsis thaliana), including ethyl methanesulfonate, fast-neutron and defined T-DNA mutants, and natural accession and populations of recombinant inbred lines from over 800 separate experiments, representing over 1,000,000 fully quantitative elemental concentrations. PiiMS is accessible at www.purdue.edu/dp/ionomics.  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