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排序方式: 共有497条查询结果,搜索用时 15 毫秒
71.
Simona Dimchevska Nikola Geskovski Gjorgji Petruševski Marina Chacorovska Riste Popeski-Dimovski Sonja Ugarkovic 《Drug development and industrial pharmacy》2017,43(3):502-510
One of the most important problems in nanoencapsulation of extremely hydrophobic drugs is poor drug loading due to rapid drug crystallization outside the polymer core. The effort to use nanoprecipitation, as a simple one-step procedure with good reproducibility and FDA approved polymers like Poly(lactic-co-glycolic acid) (PLGA) and Polycaprolactone (PCL), will only potentiate this issue. Considering that drug loading is one of the key defining characteristics, in this study we attempted to examine whether the nanoparticle (NP) core composed of two hydrophobic polymers will provide increased drug loading for 7-Ethyl-10-hydroxy-camptothecin (SN-38), relative to NPs prepared using individual polymers. D-optimal design was applied to optimize PLGA/PCL ratio in the polymer blend and the mode of addition of the amphiphilic copolymer Lutrol®F127 in order to maximize SN-38 loading and obtain NPs with acceptable size for passive tumor targeting. Drug/polymer and polymer/polymer interaction analysis pointed to high degree of compatibility and miscibility among both hydrophobic polymers, providing core configuration with higher drug loading capacity. Toxicity studies outlined the biocompatibility of the blank NPs. Increased in vitro efficacy of drug-loaded NPs compared to the free drug was confirmed by growth inhibition studies using SW-480 cell line. Additionally, the optimized NP formulation showed very promising blood circulation profile with elimination half-time of 7.4?h. 相似文献
72.
Paul Strasser Bianca Montsch Silvia Weiss Haider Sami Christoph Kugler Sonja Hager Hemma Schueffl Robert Mader Oliver Brüggemann Christian R. Kowol Manfred Ogris Petra Heffeter Ian Teasdale 《Small (Weinheim an der Bergstrasse, Germany)》2023,19(22):2300767
Bottlebrush polymers are highly promising as unimolecular nanomedicines due to their unique control over the critical parameters of size, shape and chemical function. However, since they are prepared from biopersistent carbon backbones, most known bottlebrush polymers are non-degradable and thus unsuitable for systemic therapeutic administration. Herein, we report the design and synthesis of novel poly(organo)phosphazene-g-poly(α-glutamate) (PPz-g-PGA) bottlebrush polymers with exceptional control over their structure and molecular dimensions (Dh ≈ 15–50 nm). These single macromolecules show outstanding aqueous solubility, ultra-high multivalency and biodegradability, making them ideal as nanomedicines. While well-established in polymer therapeutics, it has hitherto not been possible to prepare defined single macromolecules of PGA in these nanosized dimensions. A direct correlation was observed between the macromolecular dimensions of the bottlebrush polymers and their intracellular uptake in CT26 colon cancer cells. Furthermore, the bottlebrush macromolecular structure visibly enhanced the pharmacokinetics by reducing renal clearance and extending plasma half-lives. Real-time analysis of the biodistribution dynamics showed architecture-driven organ distribution and enhanced tumor accumulation. This work, therefore, introduces a robust, controlled synthesis route to bottlebrush polypeptides, overcoming limitations of current polymer-based nanomedicines and, in doing so, offers valuable insights into the influence of architecture on the in vivo performance of nanomedicines. 相似文献
73.
Gordana S. ?etkovi? Jasna M. ?anadanovi?-Brunet Sonja M. Djilas Vesna T. Tumbas Sini?a L. Markov Dragoljub D. Cvetkovi? 《International journal of molecular sciences》2007,8(10):1013-1027
The antioxidant activity of different Satureja montana L. subsp. kitaibelii extracts was tested by measuring their ability to scavenge reactive hydroxyl radical during the Fenton reaction, using ESR spectroscopy. Also, the influence of these extracts on lipid peroxyl radicals obtained during lipid peroxidation of: (I) sunflower oil (37 ºC, 3h) induced by 4,4′-azobis(4-cyanovaleric acid) (ACVA) and (II) liposomes induced by 2,2′-azobis(2- amidino-propane)dihydrochloride (AAPH) was studied. n-Butanol extract had the best antioxidant activity (100% at 0.5 mg/mL in Fenton reaction system; 89.21% at 5 mg/mL in system I; 83.38% at 5 mg/mL in system II). The antioxidant activities of the extracts significantly correlated with total phenolic content. The antimicrobial activity of Satureja montana L. subsp. kitaibelii extracts was investigated. Petroleum ether, chloroform and ethyl acetate extracts expressed a wide range of inhibiting activity against both grampositive and gram-negative bacteria. 相似文献
74.
Synthetic Indolactam V Analogues as Inhibitors of PAR2‐Induced Calcium Mobilization in Triple‐Negative Breast Cancer Cells 下载免费PDF全文
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
75.
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
76.
77.
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
78.
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
79.
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
80.