全文获取类型
收费全文 | 944篇 |
免费 | 83篇 |
国内免费 | 32篇 |
专业分类
电工技术 | 11篇 |
综合类 | 17篇 |
化学工业 | 603篇 |
金属工艺 | 30篇 |
机械仪表 | 18篇 |
建筑科学 | 6篇 |
轻工业 | 293篇 |
石油天然气 | 1篇 |
无线电 | 10篇 |
一般工业技术 | 17篇 |
冶金工业 | 12篇 |
原子能技术 | 3篇 |
自动化技术 | 38篇 |
出版年
2023年 | 20篇 |
2022年 | 131篇 |
2021年 | 198篇 |
2020年 | 40篇 |
2019年 | 39篇 |
2018年 | 28篇 |
2017年 | 29篇 |
2016年 | 33篇 |
2015年 | 49篇 |
2014年 | 72篇 |
2013年 | 70篇 |
2012年 | 45篇 |
2011年 | 51篇 |
2010年 | 37篇 |
2009年 | 25篇 |
2008年 | 38篇 |
2007年 | 24篇 |
2006年 | 13篇 |
2005年 | 8篇 |
2004年 | 16篇 |
2003年 | 9篇 |
2002年 | 8篇 |
2001年 | 10篇 |
2000年 | 3篇 |
1999年 | 8篇 |
1998年 | 11篇 |
1997年 | 7篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1994年 | 8篇 |
1993年 | 5篇 |
1992年 | 6篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1977年 | 1篇 |
排序方式: 共有1059条查询结果,搜索用时 31 毫秒
101.
102.
该研究以凝结芽孢杆菌(Bacillus coagulans)IPE22为研究对象,通过聚合酶链式反应(PCR)扩增获得木酮糖激酶基因Bc-XK,将其与载体pET-30a连接后,在大肠杆菌(Escherichia coli)BL21(DE3)中进行诱导表达。然后采用镍柱亲和层析纯化重组酶Bc-XK,对基因Bc-XK及其编码的蛋白质进行生信分析。结果表明,纯化后重组酶Bc-XK的酶比活力为(20.56±3.31) U/mg,热稳定性好,在60 ℃保持活力180 min以上,具有很好的工业应用潜力。Bc-XK基因含有一个1 536 bp的开放阅读框,共编码511个氨基酸,其编码的蛋白质为亲水蛋白,等电点(PI)为5.46,分子质量为56.15 kDa,二级结构中α-螺旋、无规卷曲和延伸链含量丰富,3个催化位点分别为天冬氨酸-8、苏氨酸-11、天冬氨酸-239,高度保守。 相似文献
103.
104.
肉色、嫩度、保水性等肉的品质特性一直是影响消费者购买意愿的重要因素,而肌肉能量代谢会影响肌肉的生长、发育、成熟过程,并最终影响肉的食用品质。磷酸肌酸系统、糖酵解途径和氧化磷酸化是肌肉中ATP主要来源,并在宰后不同时期发挥主要作用。动物屠宰放血后,肌肉内环境发生变化,不同的供能方式会影响能量代谢过程,从而影响肌肉转化为“肉”的过程。本文综述宰后肌肉能量代谢过程及其对肉品质的影响,并阐述腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)和沉默信息调节因子(silent information regulators,SIRTs)家族对代谢过程的影响,以期为通过能量代谢过程调控肉品质的形成提供新的思路。 相似文献
105.
该研究探讨素馨花水提物(WE)及其化学成分在3T3-L1前脂肪细胞上的降脂作用。通过将3T3-L1细胞诱导为成熟脂肪细胞,油红O染色定量和检测甘油三酯(TG)含量判断素馨花样品对脂滴的抑制作用;液质联用仪分析WE中化学成分;MTT检测素馨花及其成分对3T3-L1细胞增殖的影响;Western Blot检测AMPK、C/EBPα、FAS、ACC、CPT1、Bax、Bcl-2等蛋白表达。结果发现,WE能剂量依赖性抑制脂滴形成,其中高浓度WE(500 µg/mL)能降低中性脂质含量23.59%,降低TG含量30.20%,在脂肪积累早期作用最显著,并证明其活性成分主要是橄榄苦苷,含量为13.77%。WE及橄榄苦苷能激活AMPK(123.19%和115.98%)和其下游靶点ACC(451.06%和1 050.0%)的磷酸化、下调其下游靶点FAS(81.72%和60.50%)的蛋白表达,减少脂肪形成,提高CPT1(164.84%和292.19%)蛋白的表达,加快脂肪酸氧化;抑制C/EBPα(68.97%和34.57%)的表达,影响3T3-L1细胞分化;上调Bax(154.60%和139.37%)、下调Bcl-2(41.10%和45.62%)蛋白的表达,诱导脂肪细胞凋亡。结果提示,WE能在3T3-L1细胞分化过程早期抑制细胞生长、分化和脂肪合成并促进脂肪酸氧化从而有效抑制脂质积累,机制上可能通过调控AMPK和Bax/Bcl-2通路。 相似文献
106.
酪蛋白激酶(Protein Tyrosine Kinases,PTKs)在细胞信号转导途径中起到关键作用,已成为新型抗肿瘤活性物质的重要靶点。实验采用激酶抑制剂法对球等鞭金藻(Isochrysis galbana)的乙酸乙酯、丙酮、正戊醇和水的溶剂萃取物进行检测,结果显示,正戊醇萃取物有较明显的激酶抑制剂活性,抑制率为38.94%;对该萃取物进行薄层层析分离,以丙酮-石油醚(1∶60,v/v)为展开系统,得到Rf值为0.6610的组分,该组分对PTKs具有抑制作用,抑制率为32.21%;对此组分进行硅胶柱层析,以丙酮作为洗脱剂得到的分离组分对PTKs具有强烈的抑制作用,抑制率为86.09%,该组分同时显示出较强的细胞毒活性,这个结果预示着该组分可能是球等鞭金藻中的目的活性物质;同时,激酶抑制剂法较细胞毒活性法方便快捷,灵敏度高,是一种极具潜力的高通量筛选抗肿瘤活性物质的模型。 相似文献
107.
Arianna Giacomini Sara Taranto Sara Rezzola Sara Matarazzo Elisabetta Grillo Mattia Bugatti Alessia Scotuzzi Jessica Guerra Martina Di Trani Marco Presta Roberto Ronca 《International journal of molecular sciences》2020,21(24)
Lung cancer represents an extremely diffused neoplastic disorder with different histological/molecular features. Among the different lung tumors, non-small-cell lung cancer (NSCLC) is the most represented histotype, characterized by various molecular markers, including the expression/overexpression of the fibroblast growth factor receptor-1 (FGFR1). Thus, FGF/FGFR blockade by tyrosine kinase inhibitors (TKi) or FGF-ligand inhibitors may represent a promising therapeutic approach in lung cancers. In this study we demonstrate the potential therapeutic benefit of targeting the FGF/FGFR system in FGF-dependent lung tumor cells using FGF trapping (NSC12) or TKi (erdafitinib) approaches. The results show that inhibition of FGF/FGFR by NSC12 or erdafitinib induces apoptosis in FGF-dependent human squamous cell carcinoma NCI-H1581 and NCI-H520 cells. Induction of oxidative stress is the main mechanism responsible for the therapeutic/pro-apoptotic effect exerted by both NSC12 and erdafitinib, with apoptosis being abolished by antioxidant treatments. Finally, reduction of c-Myc protein levels appears to strictly determine the onset of oxidative stress and the therapeutic response to FGF/FGFR inhibition, indicating c-Myc as a key downstream effector of FGF/FGFR signaling in FGF-dependent lung cancers. 相似文献
108.
MASOUMEH OGHABI AVA SAFAROGHLI-AZAR ATIEH POURBAGHERI-SIGAROODI MOHAMMAD SAYYADI MOHSEN HAMIDPOUR MOHAMMAD HOSSEIN MOHAMMADI DAVOOD BASHASH 《Biocell》2020,44(2):183-192
Pathogenesis of chronic myeloid leukemia (CML) has mostly been studied with regard to the oncogenic role
of BCR/ABL fusion; however, recent disclosures have declared that the challenges with the treatment of CML patients
would not be resolved until the role of other aberrancies is ignored. Given the involvement of cyclin-dependent kinases
(CDKs) in the pathogenesis of CML, the present study aimed to investigate the effects of a multi-CDK inhibitor
AT7519 on BCR/ABL-harboring CML-derived K562 cells. Our results showed that AT7519 effectively reduced the
survival of K562 and induced its anti-proliferative effect through the induction of G2/M arrest due to elevated p21
and p27. The resulting data also revealed that either direct or indirect suppression of c-Myc using specific c-Myc
inhibitor 10058-F4 and selective PI3K inhibitor CAL-101 resulted in a superior cytotoxicity, suggesting that the
activation of PI3K pathway could attenuate antileukemic effects of the inhibitor, at least partly, through a c-Mycdependent mechanism. To the best of our knowledge, to date, no study has addressed the effect of autophagy on
CML cell response to AT7519, and, herein, we proposed for the first time that the suppression of autophagy
boosted AT7519 cytotoxicity against K562. Overall, we suggested that selective CDK inhibitor AT7519 exerted
antileukemic effect against CML cells and propose a novel therapeutic application for the inhibitor either as a single
agent or in combination with c-Myc and/or PI3K inhibitors. 相似文献
109.
Wenyuan Zhou Chasity P. Hankinson Prof. Dr. Alexander Deiters 《Chembiochem : a European journal of chemical biology》2020,21(13):1832-1836
We have developed a new tool for the optical control of cellular ATP concentrations with a photocaged adenylate kinase (Adk). The photocaged Adk is generated by substituting a catalytically essential lysine with a hydroxycoumarin-protected lysine through site-specific unnatural amino acid mutagenesis in both E. coli and mammalian cells. Caging of the critical lysine residue offers complete suppression of Adk's phosphotransferase activity and rapid restoration of its function both in vitro and in vivo upon optical stimulation. Light-activated Adk renders faster rescue of cell growth than chemically inducible expression of wild-type Adk in E. coli as well as rapid ATP depletion in mammalian cells. Thus, caging Adk provides a new tool for direct conditional perturbation of cellular ATP concentrations thereby enabling the investigation of ATP-coupled physiological events in temporally dynamic contexts. 相似文献
110.
Dr. Daniela Carbone Dr. Barbara Parrino Dr. Stella Cascioferro Camilla Pecoraro Prof. Elisa Giovannetti Dr. Veronica Di Sarno Dr. Simona Musella Dr. Giulia Auriemma Prof. Girolamo Cirrincione Prof. Patrizia Diana 《ChemMedChem》2021,16(3):537-554
A new series of topsentin analogs, in which the central imidazole ring of the natural lead was replaced by a 1,2,4-oxadiazole moiety, was efficiently synthesized. All derivatives were pre-screened for antiproliferative activity against the National Cancer Institute (NCI-60) cell lines panel. The five most potent compounds were further investigated in various pancreatic ductal adenocarcinoma (PDAC) cell lines, including SUIT-2, Capan-1, and Panc-1 cells, eliciting EC50 values in the micromolar and sub-micromolar range, associated with significant reduction of cell migration. These remarkable results might be explained by the effects of these new topsentin analogues on epithelial-to-mesenchymal transition markers, including SNAIL-1/2 and metalloproteinase-9. Moreover, flow cytometric analysis after Annexin V-FITC and propidium iodide staining demonstrated that these derivatives enhanced apoptosis of PDAC cells. Keeping with these data, the PathScan intracellular signaling and ELISA array revealed cleavage of caspase-3 and PARP and a significant inhibition of GSK3β phosphorylation, suggesting this kinase as a potential downstream target of our novel compounds. This was further supported by a specific assay for the evaluation of GSK3β activity, showing IC50 values for the most active compounds against this enzyme in the micromolar range. 相似文献