全文获取类型
收费全文 | 449篇 |
免费 | 34篇 |
专业分类
综合类 | 6篇 |
化学工业 | 134篇 |
金属工艺 | 6篇 |
机械仪表 | 3篇 |
建筑科学 | 27篇 |
能源动力 | 13篇 |
轻工业 | 78篇 |
水利工程 | 4篇 |
石油天然气 | 2篇 |
无线电 | 12篇 |
一般工业技术 | 65篇 |
冶金工业 | 61篇 |
原子能技术 | 1篇 |
自动化技术 | 71篇 |
出版年
2024年 | 1篇 |
2023年 | 8篇 |
2022年 | 16篇 |
2021年 | 22篇 |
2020年 | 13篇 |
2019年 | 13篇 |
2018年 | 8篇 |
2017年 | 11篇 |
2016年 | 24篇 |
2015年 | 15篇 |
2014年 | 22篇 |
2013年 | 29篇 |
2012年 | 34篇 |
2011年 | 49篇 |
2010年 | 23篇 |
2009年 | 34篇 |
2008年 | 24篇 |
2007年 | 16篇 |
2006年 | 16篇 |
2005年 | 19篇 |
2004年 | 10篇 |
2003年 | 12篇 |
2002年 | 11篇 |
2001年 | 6篇 |
2000年 | 5篇 |
1999年 | 5篇 |
1998年 | 3篇 |
1997年 | 6篇 |
1996年 | 2篇 |
1995年 | 8篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1984年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有483条查询结果,搜索用时 62 毫秒
71.
Synthetic Indolactam V Analogues as Inhibitors of PAR2‐Induced Calcium Mobilization in Triple‐Negative Breast Cancer Cells
下载免费PDF全文
![点击此处可从《ChemMedChem》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Dr. Jan Stein Dr. Sonja Stahn Dr. Jörg‐M. Neudörfl Julia Sperlich Prof. Dr. Hans‐Günther Schmalz Prof. Dr. Nicole Teusch 《ChemMedChem》2018,13(2):147-154
Human proteinase‐activated receptor 2 (PAR2), a transmembrane G‐protein‐coupled receptor (GPCR), is an attractive target for a novel anticancer therapy, as it plays a critical role in cell migration and invasion. Selective PAR2 inhibitors therefore have potential as anti‐metastatic drugs. Knowing that the natural product teleocidin A2 is able to inhibit PAR2 in tumor cells, the goal of the present study was to elaborate structure–activity relationships and to identify potent PAR2 inhibitors with lower activity against the adverse target, protein kinase C (PKC). For this purpose, an efficient gram‐scale total synthesis of indolactam V (i.e., the parent structure of all teleocidins) was developed, and a library of derivatives was prepared. Some compounds were indeed found to exhibit high potency as PAR2 inhibitors at low nanomolar concentrations with improved selectivity (relative to teleocidin A2). The pseudopeptidic fragment bridging the C3 and C4 positions of the indole core proved to be essential for target binding, whereas activity and target selectivity depends on the substituents at N1 or C7. This study revealed novel derivatives that show high efficacy in PAR2 antagonism combined with increased selectivity. 相似文献
72.
Although housing conditions were an integral part of the emergence of the Public Health movement, there has been relatively little research on the relationship between housing and health compared to that on social inequalities in general. This is surprising in view of the fact that one of the major links between social inequalities and health is adverse housing conditions. Findings from previous investigations in several countries of the presence of damp and mould in housing and symptoms in the occupants have indicated that the associations may well be causal. However, there have been no studies which have assessed the health of the residents before and after the elimination of dampness/mould. This paper describes a longitudinal study designed to evaluate the effects of an improved heating system on the symptoms of children living on a peripheral housing estate. The results suggested that the elimination of dampness/mould prevented a further deterioration in health rather than bringing about an improvement. The presence of other factors known to influence health status, such as financial difficulties and other housing problems, may have offset any benefits arising from the new heating system. The methodological issues that arose in conducting the study in an area of severe social disadvantage are described. It is suggested that the complexity of the interactions between bad housing and low income, should not detract attention from the need for intersectoral co‐operation to address the issue. 相似文献
73.
74.
Societal concerns and risk decisions 总被引:1,自引:0,他引:1
Societal concern is a relatively new term and refers to hazards with the capability to generate socio-political responses. Hazards invoking societal concerns pose a challenge to decision makers for they oftentimes have major policy implications yet frequently lack the analytic support affording them such elevated status. Regulators and corporate risk managers, therefore, have been confronted with the difficult question -how and to what extent should societal concerns be factored into risk management decisions? - a question which is compounded by the tendency of 'politicians' to want to accommodate these concerns. Here we first seek to explore the drivers of societal concerns prior to considering the implications for decision makers. We conclude that societal concerns stem from highly disparate causes, are not necessarily originated by the public as is often implied, and as such have markedly differing legitimacies. Furthermore, we note that attempts to incorporate societal concerns into risk decisions raise a host of methodological, political, and ethical issues which suggest, at the very least, that deep caution is required, especially where policy implications are high. 相似文献
75.
Glucoamylase from Thermoanaerobacterium thermosaccharolyticum ATCC 7956 (DSM 571) was produced in extracellular form. It was purified to homogeneity by two separate methods, one with two chromatographic steps and the other with three. This glucoamylase is closely related to glucoamylases from Clostridium sp. G0005 and T. thermosaccharolyticum DSM 572. Activities and KM values with maltose substrate are less than one‐tenth and about fourfold, respectively, those of Aspergillus niger glucoamylase. T. thermosaccharolyticum glucoamylase is about twenty times as thermostable as A. niger glucoamylase and its optimal pH is somewhat higher at 4.9; however, it is produced in much lower activities. Sorbitol strongly stabilizes A. niger glucoamylase. 相似文献
76.
Reham Atallah Juergen Gindlhuber Wolfgang Platzer Thomas Brnthaler Eva Tatzl Wolfgang Toller Jasmin Strutz Sonja Rittchen Petra Luschnig Ruth Birner-Gruenberger Christian Wadsack Akos Heinemann 《International journal of molecular sciences》2021,22(21)
Placental hypervascularization has been reported in pregnancy-related pathologies such as gestational diabetes mellitus (GDM). Nevertheless, the underlying causes behind this abnormality are not well understood. In this study, we addressed the expression of SUCNR1 (cognate succinate receptor) in human placental endothelial cells and hypothesized that the succinate–SUCNR1 axis might play a role in the placental hypervascularization reported in GDM. We measured significantly higher succinate levels in placental tissue lysates from women with GDM relative to matched controls. In parallel, SUCNR1 protein expression was upregulated in GDM tissue lysates as well as in isolated diabetic fetoplacental arterial endothelial cells (FpECAds). A positive correlation of SUCNR1 and vascular endothelial growth factor (VEGF) protein levels in tissue lysates indicated a potential link between the succinate–SUCNR1 axis and placental angiogenesis. In our in vitro experiments, succinate prompted hallmarks of angiogenesis in human umbilical vein endothelial cells (HUVECs) such as proliferation, migration and spheroid sprouting. These results were further validated in fetoplacental arterial endothelial cells (FpECAs), where succinate induced endothelial tube formation. VEGF gene expression was increased in response to succinate in both HUVECs and FpECAs. Yet, knockdown of SUCNR1 in HUVECs led to suppression of VEGF gene expression and abrogated the migratory ability and wound healing in response to succinate. In conclusion, our data underline SUCNR1 as a promising metabolic target in human placenta and as a potential driver of enhanced placental angiogenesis in GDM. 相似文献
77.
Introduction
This study investigated the modality, type and duration of contact lens wear as well as compliance and hygiene related issues (hand and case hygiene, use of tap water, dozing and overnight wear) in the UK and Germany. Questionnaires were collected anonymously from 417 UK and 767 German patients attending optometric practices for contact lens appointments. It is the seventh of a series of contact lens wearer profiles conducted since 2000.Results
The proportion of rigid gas permeable lenses worn was significantly higher at 55.4% in Germany, compared to 16.1% in the UK. Overall, a significantly larger proportion of German participants used tap water to rinse their lenses and cases (P < 0.001). Also, German respondents changed their lens cases less frequently (p < 0.001). Fewer UK than German respondents stated they washed their hands before lens insertion (p = 0.009), removal (p = 0.01), before eating (p < 0.001). German participants were less likely to wash their hands before preparing food (p = 0.042) and after using the toilet (p = 0.002). The two sample groups differed significantly regarding the care regimens they used for their CLs (p < 0.001).Conclusion
The differences between Germany and the UK highlighted in this study were caused by differences in legal regulations, plumbing and practitioners’ guidance. Although many of the questions relating to hygiene differed statistically between the two participating sample groups, the absolute differences in figures were not considered to be large. 相似文献78.
Simultaneous quantitative analysis of metabolites using ion-pair liquid chromatography-electrospray ionization mass spectrometry 总被引:1,自引:0,他引:1
Coulier L Bas R Jespersen S Verheij E van der Werf MJ Hankemeier T 《Analytical chemistry》2006,78(18):6573-6582
We have developed an analytical method, consisting of ion-pair liquid chromatography coupled to electrospray ionization mass spectrometry (IP-LC-ESI-MS), for the simultaneous quantitative analysis of several key classes of polar metabolites, like nucleotides, coenzyme A esters, sugar nucleotides, and sugar bisphosphates. The use of the ion-pair agent hexylamine and optimization of the pH of the mobile phases were critical parameters in obtaining good retention and peak shapes of many of the above-mentioned polar and acidic metabolites that are impossible to analyze using standard reversed-phase LC/MS. Optimum conditions were found when using a gradient from 5 mM hexylamine in water (pH 6.3) to 90% methanol/10% 10 mM ammonium acetate (pH 8.5). The IP-LC-ESI-MS method was extensively validated by determining the linearity (R2 > 0.995), sensitivity (limit of detection 0.1-1 ng), repeatability, and reproducibility (relative standard deviation <10%). The IP-LC-ESI-MS method was shown to be a useful tool for microbial metabolomics, i.e., the comprehensive quantitative analysis of metabolites in extracts of microorganisms, and for the determination of the energy charge, i.e., the cellular energy status, as an overall quality measure for the sample workup and analytical protocols. 相似文献
79.
Yeasts isolated from three varieties of grapes cultivated in different locations of the Dolenjska vine-growing region, Slovenia 总被引:1,自引:0,他引:1
Raspor P Milek DM Polanc J Mozina SS Cadez N 《International journal of food microbiology》2006,109(1-2):97-102
The number and diversity of yeasts on grape berry surfaces are influenced by several factors, such as grape variety, degree of grape maturity at harvest, climatological conditions, geographic location, physical damage of grapes, the intensity of pest management etc. Cvicek is a typical Slovene wine, which has obtained a special protection under the Slovene Wine Law for its geographical origin. This blended red wine is produced from different grape varieties (Vitis vinifera L.), mostly from red grapes of Zametovka and Modra frankinja and from white grapes of Kraljevina. The aim of this study was to evaluate the impact of geographical locations in the Dolenjska vine-growing region and to obtain precise information about the influence of different grape varieties on the composition of yeast community on grape berries. The restriction fragment length polymorphism of PCR-amplified fragments from the rDNA gene cluster (PCR RFLP of rDNA) has been used for the differentiation of yeast species. The standard identification procedure has been performed on representative strains that shared identical RFLP profiles. The number of yeasts and yeast species isolated varied according to different grape varieties, Zametovka, Modra frankinja and Kraljevina (V. vinifera L.) and according to different sampling location. On the surface of grape berries 13 different yeast species have been identified. Saccharomyces cerevisiae has not been found. 相似文献
80.