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1.
Agnieszka Krawczyk-ebek Monika Dymarska Tomasz Janeczko Edyta Kostrzewa-Susow 《International journal of molecular sciences》2022,23(10)
Flavonoid compounds exhibit numerous biological activities and significantly impact human health. The presence of methyl or glucosyl moieties attached to the flavonoid core remarkably modifies their physicochemical properties and improves intestinal absorption. Combined chemical and biotechnological methods can be applied to obtain such derivatives. In the presented study, 4′-methylflavanone was synthesized and biotransformed in the cultures of three strains of entomopathogenic filamentous fungi, i.e., Isaria fumosorosea KCH J2, Beauveria bassiana KCH J1.5, and Isaria farinosa KCH J2.1. The microbial transformation products in the culture of I. fumosorosea KCH J2, flavanone 4′-methylene-O-β-D-(4″-O-methyl)-glucopyranoside, 2-phenyl-(4′-hydroxymethyl)-4-hydroxychromane, and flavanone 4′-carboxylic acid were obtained. Biotransformation of 4′-methylflavanone in the culture of B. bassiana KCH J1.5 resulted in the formation of one main product, i.e., flavanone 4′-methylene-O-β-D-(4″-O-methyl)-glucopyranoside. In the case of I. farinosa KCH J2.6 as a biocatalyst, three products, i.e., flavanone 4′-methylene-O-β-D-(4″-O-methyl)-glucopyranoside, flavanone 4′-carboxylic acid, and 4′-hydroxymethylflavanone 4-O-β-D-(4″-O-methyl)-glucopyranoside were obtained. The Swiss-ADME online simulations confirmed the increase in water solubility of 4′-methylflavanone glycosides and analyses performed using the Way2Drug Pass Online prediction tool indicated that flavanone 4′-methylene-O-β-D-(4″-O-methyl)-glucopyranoside and 4′-hydroxymethylflavanone 4-O-β-D-(4″-O-methyl)-glucopyranoside, which had not been previously reported in the literature, are promising anticarcinogenic, antimicrobial, and hepatoprotective agents. 相似文献
2.
Sandra Brasil Mariateresa Allocca Salvador C. M. Magrinho Inês Santos Madalena Raposo Rita Francisco Carlota Pascoal Tiago Martins Paula A. Videira Florbela Pereira Giuseppina Andreotti Jaak Jaeken Kristin A. Kantautas Ethan O. Perlstein Vanessa dos Reis Ferreira 《International journal of molecular sciences》2022,23(15)
Advances in research have boosted therapy development for congenital disorders of glycosylation (CDG), a group of rare genetic disorders affecting protein and lipid glycosylation and glycosylphosphatidylinositol anchor biosynthesis. The (re)use of known drugs for novel medical purposes, known as drug repositioning, is growing for both common and rare disorders. The latest innovation concerns the rational search for repositioned molecules which also benefits from artificial intelligence (AI). Compared to traditional methods, drug repositioning accelerates the overall drug discovery process while saving costs. This is particularly valuable for rare diseases. AI tools have proven their worth in diagnosis, in disease classification and characterization, and ultimately in therapy discovery in rare diseases. The availability of biomarkers and reliable disease models is critical for research and development of new drugs, especially for rare and heterogeneous diseases such as CDG. This work reviews the literature related to repositioned drugs for CDG, discovered by serendipity or through a systemic approach. Recent advances in biomarkers and disease models are also outlined as well as stakeholders’ views on AI for therapy discovery in CDG. 相似文献
3.
Iwona Radziejewska Katarzyna Supruniuk Micha Tomczyk Wiktoria Izdebska Magorzata Borzym-Kluczyk Anna Bielawska Krzysztof Bielawski Anna Galicka 《International journal of molecular sciences》2022,23(15)
Abnormal glycosylation of cancer cells is considered a key factor of carcinogenesis related to growth, proliferation, migration and invasion of tumor cells. Many plant-based polyphenolic compounds reveal potential anti-cancer properties effecting cellular signaling systems. Herein, we assessed the effects of phenolic acid, p-coumaric acid and flavonoids such as kaempferol, astragalin or tiliroside on expression of selected cancer-related glycoforms and enzymes involved in their formation in AGS gastric cancer cells. The cells were treated with 80 and 160 µM of the compounds. RT-PCR, Western blotting and ELISA tests were performed to determine the influence of polyphenolics on analyzed factors. All the examined compounds inhibited the expression of MUC1, ST6GalNAcT2 and FUT4 mRNAs. C1GalT1, St3Gal-IV and FUT4 proteins as well as MUC1 domain, Tn and sialyl T antigen detected in cell lysates were also lowered. Both concentrations of kaempferol, astragalin and tiliroside also suppressed ppGalNAcT2 and C1GalT1 mRNAs. MUC1 cytoplasmic domain, sialyl Tn, T antigens in cell lysates and sialyl T in culture medium were inhibited only by kaempferol and tiliroside. Nuclear factor NF-κB mRNA expression decreased after treatment with both concentrations of kaempferol, astragalin and tiliroside. NF-κB protein expression was inhibited by kaempferol and tiliroside. The results indicate the rationality of application of examined polyphenolics as potential preventive agents against gastric cancer development. 相似文献
4.
基于核Fisher判别分析的蛋白质氧链糖基化位点的预测 总被引:1,自引:0,他引:1
以各种窗口长度的蛋白质样本序列为研究对象,实验样本用稀疏编码方式编码,使用核Fisher判别分析(KFDA)的方法来预测蛋白质氧链糖基化位点。首先通过非线性映射(由核函数隐含定义)将样本映射到特征空间,然后在特征空间中用Fisher判别分析进行分类。进一步,用多数投票策略对各种窗口下的分类器进行组合以综合多个窗口的优势。实验结果表明,使用组合KFDA的方法预测的效果优于FDA和PCA以及单个KFDA分类器的预测效果,预测准确率为86.5%。 相似文献
5.
6.
Barbara Eleni Rosato Roberta Marra Vanessa DOnofrio Federica Del Giudice Simone Della Monica Achille Iolascon Immacolata Andolfo Roberta Russo 《International journal of molecular sciences》2022,23(3)
Biallelic pathogenic variants in the SEC23B gene cause congenital dyserythropoietic anemia type II (CDA II), a rare hereditary disorder hallmarked by ineffective erythropoiesis, hemolysis, erythroblast morphological abnormalities, and hypo-glycosylation of some red blood cell membrane proteins. Abnormalities in SEC23B, which encodes the homonymous cytoplasmic COPII (coat protein complex II) component, disturb the endoplasmic reticulum to Golgi trafficking and affect different glycosylation pathways. The most harmful complication of CDA II is the severe iron overload. Within our case series (28 CDA II patients), approximately 36% of them exhibit severe iron overload despite mild degree of anemia and slightly increased levels of ERFE (the only erythroid regulator of hepcidin suppression). Thus, we hypothesized a direct role of SEC23B loss-of-function in the pathomechanism of hepatic iron overload. We established a hepatic cell line, HuH7, stably silenced for SEC23B. In silenced cells, we observed significant alterations of the iron status, due to both the alteration in BMP/SMADs pathway effectors and a reduced capability to sense BMP6 stimulus. We demonstrated that the loss-of-function of SEC23B is responsible of the impairment in glycosylation of the membrane proteins involved in the activation of the BMP/SMADs pathway with subsequent hepcidin suppression. Most of these data were confirmed in another hepatic cell line, HepG2, stably silenced for SEC23B. Our findings suggested that the pathogenic mechanism of iron overload in CDA II is associated to both ineffective erythropoiesis and to a specific involvement of SEC23B pathogenic variants at hepatic level. Finally, we demonstrated the ability of SEC23B paralog, i.e., SEC23A, to rescue the hepcidin suppression, highlighting the functional overlap between the two SEC23 paralogs in human hepatic cells. 相似文献
7.
Anna Sadakierska-Chudy Pawe Szymanowski Arleta Lebioda Rafa Poski 《International journal of molecular sciences》2022,23(7)
Rectal prolapse is influenced by many factors including connective tissue dysfunction. Currently, there is no data about genetic contribution in the etiology of this disorder. In this study, we performed trio whole-exome sequencing in an 11-year-old girl with mucosal rectal prolapse and her parents and sibling. Genetic testing revealed a novel heterozygous missense variant c.1406G>T; p.G469V in exon 11 of the COLGALT2 gene encoding the GLT25 D2 enzyme. Sanger sequencing confirmed this variant only in the patient while the mother, father and sister showed a wild-type sequence. The pathogenicity of the novel variant was predicted using 10 different in silico tools that classified it as pathogenic. Further, in silico prediction, according to Phyre2, Project HOPE, I-Mutant3.0 and MutPred2 showed that the missense variant can decrease protein stability and cause alterations in the physical properties of amino acids resulting in structural and functional changes of the GLT25D2 protein. In conclusion, the present study identifies a previously unknown missense mutation in the COLGALT2 gene that encodes the enzyme involved in collagen glycosylation. The clinical features observed in the patient and the results of in silico analysis suggest that the new genetic variant can be pathogenic. 相似文献
8.
9.
糖基化反应条件对乳清蛋白——麦芽糖复合物抗原性的影响 总被引:2,自引:0,他引:2
研究了将麦芽糖通过糖基化引入到乳清蛋白制备乳清蛋白-麦芽糖,用间接竞争ELISA法测定不同反应时间不同质量比的乳清蛋白-麦芽糖中α-乳白蛋白和β-乳球蛋白的抗原性的变化。结果表明,糖基化能有效降低α-乳白蛋白和β-乳球蛋白的抗原性,α-乳白蛋白的抗原性可以从26.2 mg/L降低到14.4 mg/L,β-乳球蛋白的抗原性可以从95.1 mg/L降低到22.4 mg/L。反应时间对不同质量比的乳清蛋白-麦芽糖中α-乳白蛋白和β-乳球蛋白的抗原性有较大影响。蛋白与糖的质量比为1~8时,反应相同时间的乳清蛋白-麦芽糖中α-乳白蛋白和β-乳球蛋白的抗原性随蛋白与糖的质量比的下降而下降。 相似文献
10.