全文获取类型
收费全文 | 639篇 |
免费 | 71篇 |
专业分类
电工技术 | 4篇 |
化学工业 | 342篇 |
金属工艺 | 5篇 |
机械仪表 | 11篇 |
建筑科学 | 25篇 |
能源动力 | 9篇 |
轻工业 | 137篇 |
水利工程 | 2篇 |
无线电 | 24篇 |
一般工业技术 | 72篇 |
冶金工业 | 11篇 |
自动化技术 | 68篇 |
出版年
2024年 | 1篇 |
2023年 | 7篇 |
2022年 | 85篇 |
2021年 | 103篇 |
2020年 | 26篇 |
2019年 | 24篇 |
2018年 | 39篇 |
2017年 | 26篇 |
2016年 | 35篇 |
2015年 | 39篇 |
2014年 | 43篇 |
2013年 | 42篇 |
2012年 | 37篇 |
2011年 | 39篇 |
2010年 | 29篇 |
2009年 | 30篇 |
2008年 | 26篇 |
2007年 | 10篇 |
2006年 | 15篇 |
2005年 | 23篇 |
2004年 | 6篇 |
2003年 | 6篇 |
2002年 | 5篇 |
2001年 | 3篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1994年 | 3篇 |
排序方式: 共有710条查询结果,搜索用时 46 毫秒
71.
Ruth U Barbante C Bigler M Delmonte B Fischer H Gabrielli P Gaspari V Kaufmann P Lambert F Maggi V Marino F Petit JR Udisti R Wagenbach D Wegner A Wolff EW 《Environmental science & technology》2008,42(15):5675-5681
To improve quantitative interpretation of ice core aeolian dust records, a systematic methodological comparison was made. This involved methods for water-insoluble particle counting (Coulter counter and laser-sensing particle detector), soluble ion analysis (ion chromatography and continuous flow analysis), elemental analysis (inductively coupled plasma mass spectroscopy at pH 1 and after full acid digestion), and water-insoluble elemental analysis (proton induced X-ray emission). Antarctic ice core samples covering the last deglaciation from the EPICA Dome C (EDC) and the EPICA Dronning Maud Land (EDML) cores were used. All methods correlate very well among each other, but the ratios of glacial age to Holocene concentrations, which are typically a factor approximately 100, differ between the methods by up to a factor of 2 with insoluble particles showing the largest variability. The recovery of ICP-MS measurements depends on the digestion method and is differentfor different elements and during different climatic periods. EDC and EDML samples have similar dust composition, which suggests a common dust source or a common mixture of sources for the two sites. The analyzed samples further reveal a change of dust composition during the last deglaciation. 相似文献
72.
Lorenzo Allegri Francesca Capriglione Valentina Maggisano Giuseppe Damante Federica Baldan 《International journal of molecular sciences》2021,22(15)
ATC is a very rare, but extremely aggressive form of thyroid malignancy, responsible for the highest mortality rate registered for thyroid cancer. In patients without known genetic aberrations, the current treatment is still represented by palliative surgery and systemic mono- or combined chemotherapy, which is often not fully effective for the appearance of drug resistance. Comprehension of the mechanisms involved in the development of the resistance is therefore an urgent issue to suggest novel therapeutic approaches for this very aggressive malignancy. In this study, we created a model of anaplastic thyroid cancer (ATC) cells resistant to paclitaxel and investigated the characteristics of these cells by analyzing the profile of gene expression and comparing it with that of paclitaxel-sensitive original ATC cell lines. In addition, we evaluated the effects of Dihydrotanshinone I (DHT) on the viability and invasiveness of paclitaxel-resistant cells. ATC paclitaxel-resistant cells highlighted an overexpression of ABCB1 and a hyper-activation of the NF-κB compared to sensitive cells. DHT treatment resulted in a reduction of viability and clonogenic ability of resistant cells. Moreover, DHT induces a decrement of NF-κB activity in SW1736-PTX and 8505C-PTX cells. In conclusion, to the best of our knowledge, the results of the present study are the first to demonstrate the antitumor effects of DHT on ATC cells resistant to Paclitaxel in vitro. 相似文献
73.
Federica Armas Adriana Di Stasi Mario Mardirossian Antonello A. Romani Monica Benincasa Marco Scocchi 《International journal of molecular sciences》2021,22(15)
The emergence of multidrug-resistant bacteria is a worldwide health problem. Antimicrobial peptides have been recognized as potential alternatives to conventional antibiotics, but still require optimization. The proline-rich antimicrobial peptide Bac7(1-16) is active against only a limited number of Gram-negative bacteria. It kills bacteria by inhibiting protein synthesis after its internalization, which is mainly supported by the bacterial transporter SbmA. In this study, we tested two different lipidated forms of Bac7(1-16) with the aim of extending its activity against those bacterial species that lack SbmA. We linked a C12-alkyl chain or an ultrashort cationic lipopeptide Lp-I to the C-terminus of Bac7(1-16). Both the lipidated Bac-C12 and Bac-Lp-I forms acquired activity at low micromolar MIC values against several Gram-positive and Gram-negative bacteria. Moreover, unlike Bac7(1-16), Bac-C12, and Bac-Lp-I did not select resistant mutants in E. coli after 14 times of exposure to sub-MIC concentrations of the respective peptide. We demonstrated that the extended spectrum of activity and absence of de novo resistance are likely related to the acquired capability of the peptides to permeabilize cell membranes. These results indicate that C-terminal lipidation of a short proline-rich peptide profoundly alters its function and mode of action and provides useful insights into the design of novel broad-spectrum antibacterial agents. 相似文献
74.
Kashif Ali Federica Maltese Ana Margarida Fortes Maria Salomé Pais Young Hae Choi Robert Verpoorte 《Food chemistry》2011
1H nuclear magnetic resonance (NMR) was applied for the metabolic profiling of grapes from three Portuguese cultivars including ‘Trincadeira’, ‘Aragonês’, and ‘Touriga Nacional’, at four developmental stages. Two kinds of extraction methods including deuterated NMR solvent extraction and solid phase extraction (SPE) were used for the metabolomic analysis and all the metabolites detected in 1H NMR were elucidated by two-dimensional NMR techniques as well as the in-house NMR chemical shift database. Multivariate data analyses were also performed to identify overall metabolic differences. Trincadeira was found different from the other two cultivars, having low phenolic contents as compared to other cultivars. The initial stages showed comparatively high phenolics and organic acid contents like caftaric and malic acid while the later stages showed higher glucose and fructose levels. Veraison was found to be a metabolically critical stage of berry development. On the basis of these findings distribution of metabolites among different cultivars at different developmental stages is discussed. 相似文献
75.
Ginevra Zanni Cheng-Tsung Hsiao Ssu-Ju Fu Chih-Yung Tang Alessandro Capuano Luca Bosco Federica Graziola Emanuele Bellacchio Serenella Servidei Guido Primiano Bing-Wen Soong Chung-Jiuan Jeng 《International journal of molecular sciences》2021,22(9)
KCND3 encodes the voltage-gated potassium channel KV4.3 that is highly expressed in the cerebellum, where it regulates dendritic excitability and calcium influx. Loss-of-function KV4.3 mutations have been associated with dominant spinocerebellar ataxia (SCA19/22). By targeted NGS sequencing, we identified two novel KCND3 missense variants of the KV4.3 channel: p.S347W identified in a patient with adult-onset pure cerebellar syndrome and p.W359G detected in a child with congenital nonprogressive ataxia. Neuroimaging showed mild cerebellar atrophy in both patients. We performed a two-electrode voltage-clamp recording of KV4.3 currents in Xenopus oocytes: both the p.G345V (previously reported in a SCA19/22 family) and p.S347W mutants exhibited reduced peak currents by 50%, while no K+ current was detectable for the p.W359G mutant. We assessed the effect of the mutations on channel gating by measuring steady-state voltage-dependent activation and inactivation properties: no significant alterations were detected in p.G345V and p.S347W disease-associated variants, compared to controls. KV4.3 expression studies in HEK293T cells showed 53% (p.G345V), 45% (p.S347W) and 75% (p.W359G) reductions in mutant protein levels compared with the wildtype. The present study broadens the spectrum of the known phenotypes and identifies additional variants for KCND3-related disorders, outlining the importance of SCA gene screening in early-onset and congenital ataxia. 相似文献
76.
Prof. Chiara Brullo Dr. Federica Rapetti Prof. Silvana Alfei Dr. Irena Maric Dr. Francesca Rizzelli Dr. Marina Mapelli Dr. Camillo Rosano Dr. Maurizio Viale Prof. Olga Bruno 《ChemMedChem》2020,15(11):961-969
Even though immunotherapy has radically changed the search for anticancer therapies, there are still many different pathways that are open to intervention with traditional small molecules. To expand our investigation in the anticancer field, we report here a new series of compounds in which our previous pyrazole and imidazopyrazole scaffolds are linked to a differently decorated phenyl ring through an acylhydrazone linker. Preliminary tests on the library were performed at the National Cancer Institute (USA) against the full NCI 60 cell panel. The best compounds among the imidazopyrazole series were then tested by immunofluorescence staining for their inhibition of cell proliferation, apoptosis induction, and their effect on the cell cycle and on microtubules. Two compounds, in particular 4-benzyloxy-3-methoxybenzyliden imidazopyrazole-7-carbohydrazide showed good growth inhibition, with IC50 values in the low-micromolar range, and induced apoptosis. Both compounds altered the cell-cycle phases with the appearance of polyploid cells. Immunofluorescence analysis evidenced microtubules alterations; tubulin polymerization assays and docking studies suggested the tubulin system to be the possible, although not exclusive, target of the new acylhydrazone series reported here. 相似文献
77.
78.
Alessia DAloia Federica Arrigoni Renata Tisi Alessandro Palmioli Michela Ceriani Valentina Artusa Cristina Airoldi Giuseppe Zampella Barbara Costa Laura Cipolla 《International journal of molecular sciences》2020,21(23)
Palmitoylethanolamide (PEA) belongs to the class of N-acylethanolamine and is an endogenous lipid potentially useful in a wide range of therapeutic areas; products containing PEA are licensed for use in humans as a nutraceutical, a food supplement, or food for medical purposes for its analgesic and anti-inflammatory properties demonstrating efficacy and tolerability. However, the exogenously administered PEA is rapidly inactivated; in this process, fatty acid amide hydrolase (FAAH) plays a key role both in hepatic metabolism and in intracellular degradation. So, the aim of the present study was the design and synthesis of PEA analogues that are more resistant to FAAH-mediated hydrolysis. A small library of PEA analogues was designed and tested by molecular docking and density functional theory calculations to find the more stable analogue. The computational investigation identified RePEA as the best candidate in terms of both synthetic accessibility and metabolic stability to FAAH-mediated hydrolysis. The selected compound was synthesized and assayed ex vivo to monitor FAAH-mediated hydrolysis and to confirm its anti-inflammatory properties. 1H-NMR spectroscopy performed on membrane samples containing FAAH in integral membrane protein demonstrated that RePEA is not processed by FAAH, in contrast with PEA. Moreover, RePEA retains PEA’s ability to inhibit LPS-induced cytokine release in both murine N9 microglial cells and human PMA-THP-1 cells. 相似文献
79.
Gloria Ravegnini Bruno Fosso Viola Di Saverio Giulia Sammarini Federica Zanotti Giulio Rossi Monica Ricci Federica DAmico Giorgia Valori Antonella Ioli Silvia Turroni Patrizia Brigidi Patrizia Hrelia Sabrina Angelini 《International journal of molecular sciences》2020,21(24)
Gastric cancer (GC) is the fifth most prevalent cancer worldwide and the third leading cause of global cancer mortality. With the advances of the omic studies, a heterogeneous GC landscape has been revealed, with significant molecular diversity. Given the multifaceted nature of GC, identification of different patient subsets with prognostic and/or predictive outcomes is a key aspect to allow tailoring of specific treatments. Recently, the involvement of the microbiota in gastric carcinogenesis has been described. To deepen this aspect, we compared microbiota composition in signet-ring cell carcinoma (SRCC) and adenocarcinoma (ADC), two distinct GC subtypes. To this purpose, 10 ADC and 10 SRCC and their paired non-tumor (PNT) counterparts were evaluated for microbiota composition through 16S rRNA analysis. Weighted and unweighted UniFrac and Bray–Curtis dissimilarity showed significant community-level separation between ADC and SRCC. Through the LEfSe (linear discriminant analysis coupled with effect size) tool, we identified potential microbial biomarkers associated with GC subtypes. In particular, SRCCs were significantly enriched in the phyla Fusobacteria, Bacteroidetes, Patescibacteria, whereas in the ADC type, Proteobacteria and Acidobacteria phyla were found. Overall, our data add new insights into GC heterogeneity and may contribute to deepening the GC classification. 相似文献
80.
Nicola Curci Andrea Strazzulli Roberta Iacono Federica De Lise Luisa Maurelli Mauro Di Fenza Beatrice Cobucci-Ponzano Marco Moracci 《International journal of molecular sciences》2021,22(7)
In the field of biocatalysis and the development of a bio-based economy, hemicellulases have attracted great interest for various applications in industrial processes. However, the study of the catalytic activity of the lignocellulose-degrading enzymes needs to be improved to achieve the efficient hydrolysis of plant biomasses. In this framework, hemicellulases from hyperthermophilic archaea show interesting features as biocatalysts and provide many advantages in industrial applications thanks to their stability in the harsh conditions encountered during the pretreatment process. However, the hemicellulases from archaea are less studied compared to their bacterial counterpart, and the activity of most of them has been barely tested on natural substrates. Here, we investigated the hydrolysis of xyloglucan oligosaccharides from two different plants by using, both synergistically and individually, three glycoside hydrolases from Saccharolobus solfataricus: a GH1 β-gluco-/β-galactosidase, a α-fucosidase belonging to GH29, and a α-xylosidase from GH31. The results showed that the three enzymes were able to release monosaccharides from xyloglucan oligosaccharides after incubation at 65 °C. The concerted actions of β-gluco-/β-galactosidase and the α-xylosidase on both xyloglucan oligosaccharides have been observed, while the α-fucosidase was capable of releasing all α-linked fucose units from xyloglucan from apple pomace, representing the first GH29 enzyme belonging to subfamily A that is active on xyloglucan. 相似文献