全文获取类型
收费全文 | 6402篇 |
免费 | 487篇 |
国内免费 | 11篇 |
专业分类
电工技术 | 58篇 |
综合类 | 10篇 |
化学工业 | 2833篇 |
金属工艺 | 78篇 |
机械仪表 | 86篇 |
建筑科学 | 263篇 |
矿业工程 | 35篇 |
能源动力 | 160篇 |
轻工业 | 1130篇 |
水利工程 | 41篇 |
石油天然气 | 35篇 |
无线电 | 261篇 |
一般工业技术 | 937篇 |
冶金工业 | 327篇 |
原子能技术 | 15篇 |
自动化技术 | 631篇 |
出版年
2024年 | 16篇 |
2023年 | 112篇 |
2022年 | 673篇 |
2021年 | 776篇 |
2020年 | 231篇 |
2019年 | 211篇 |
2018年 | 254篇 |
2017年 | 207篇 |
2016年 | 263篇 |
2015年 | 224篇 |
2014年 | 272篇 |
2013年 | 449篇 |
2012年 | 374篇 |
2011年 | 412篇 |
2010年 | 276篇 |
2009年 | 274篇 |
2008年 | 276篇 |
2007年 | 243篇 |
2006年 | 214篇 |
2005年 | 152篇 |
2004年 | 139篇 |
2003年 | 113篇 |
2002年 | 99篇 |
2001年 | 55篇 |
2000年 | 47篇 |
1999年 | 56篇 |
1998年 | 37篇 |
1997年 | 43篇 |
1996年 | 44篇 |
1995年 | 35篇 |
1994年 | 36篇 |
1993年 | 32篇 |
1992年 | 27篇 |
1991年 | 16篇 |
1990年 | 23篇 |
1989年 | 11篇 |
1988年 | 18篇 |
1987年 | 14篇 |
1986年 | 7篇 |
1985年 | 18篇 |
1984年 | 16篇 |
1983年 | 17篇 |
1982年 | 6篇 |
1981年 | 11篇 |
1980年 | 11篇 |
1979年 | 9篇 |
1977年 | 8篇 |
1976年 | 5篇 |
1974年 | 4篇 |
1966年 | 5篇 |
排序方式: 共有6900条查询结果,搜索用时 31 毫秒
991.
Sara Nava Daniela Lisini Simona Frigerio Anna Bersano 《International journal of molecular sciences》2021,22(22)
Dendritic cells (DCs) are immune specialized cells playing a critical role in promoting immune response against antigens, and may represent important targets for therapeutic interventions in cancer. DCs can be stimulated ex vivo with pro-inflammatory molecules and loaded with tumor-specific antigen(s). Protocols describing the specific details of DCs vaccination manufacturing vary widely, but regardless of the employed protocol, the DCs vaccination safety and its ability to induce antitumor responses is clearly established. Many years of studies have focused on the ability of DCs to provide overall survival benefits at least for a selection of cancer patients. Lessons learned from early trials lead to the hypothesis that, to improve the efficacy of DCs-based immunotherapy, this should be combined with other treatments. Thus, the vaccine’s ultimate role may lie in the combinatorial approaches of DCs-based immunotherapy with chemotherapy and radiotherapy, more than in monotherapy. In this review, we address some key questions regarding the integration of DCs vaccination with multimodality therapy approaches for cancer treatment paradigms. 相似文献
992.
Valentina Latina Giacomo Giacovazzo Pietro Calissano Anna Atlante Federico La Regina Francesca Malerba Marco DellAquila Egidio Stigliano Bijorn Omar Balzamino Alessandra Micera Roberto Coccurello Giuseppina Amadoro 《International journal of molecular sciences》2021,22(22)
Tau cleavage plays a crucial role in the onset and progression of Alzheimer’s Disease (AD), a widespread neurodegenerative disease whose incidence is expected to increase in the next years. While genetic and familial forms of AD (fAD) occurring early in life represent less than 1%, the sporadic and late-onset ones (sAD) are the most common, with ageing being an important risk factor. Intracerebroventricular (ICV) infusion of streptozotocin (STZ)—a compound used in the systemic induction of diabetes due to its ability to damage the pancreatic β cells and to induce insulin resistance—mimics in rodents several behavioral, molecular and histopathological hallmarks of sAD, including memory/learning disturbance, amyloid-β (Aβ) accumulation, tau hyperphosphorylation, oxidative stress and brain glucose hypometabolism. We have demonstrated that pathological truncation of tau at its N-terminal domain occurs into hippocampi from two well-established transgenic lines of fAD animal models, such as Tg2576 and 3xTg mice, and that it’s in vivo neutralization via intravenous (i.v.) administration of the cleavage-specific anti-tau 12A12 monoclonal antibody (mAb) is strongly neuroprotective. Here, we report the therapeutic efficacy of 12A12mAb in STZ-infused mice after 14 days (short-term immunization, STIR) and 21 days (long-term immunization regimen, LTIR) of i.v. delivery. A virtually complete recovery was detected after three weeks of 12A12mAb immunization in both novel object recognition test (NORT) and object place recognition task (OPRT). Consistently, three weeks of this immunization regimen relieved in hippocampi from ICV-STZ mice the AD-like up-regulation of amyloid precursor protein (APP), the tau hyperphosphorylation and neuroinflammation, likely due to modulation of the PI3K/AKT/GSK3-β axis and the AMP-activated protein kinase (AMPK) activities. Cerebral oxidative stress, mitochondrial impairment, synaptic and histological alterations occurring in STZ-infused mice were also strongly attenuated by 12A12mAb delivery. These results further strengthen the causal role of N-terminal tau cleavage in AD pathogenesis and indicate that its specific neutralization by non-invasive administration of 12A12mAb can be a therapeutic option for both fAD and sAD patients, as well as for those showing type 2 diabetes as a comorbidity. 相似文献
993.
994.
Alessia Felici Daniele Di Mascolo Miguel Ferreira Simone Lauciello Luca Bono Andrea Armirotti Arunkumar Pitchaimani Anna Lisa Palange Paolo Decuzzi 《Nano Research》2022,(1):482-491
Taxane efficacy in triple negative breast cancer(TNBC)is limited by insufficient tumor accumulation and severe off-target effects.Nanomedicines offer a unique opportunity to enhance the anti-cancer potency of this drug.Here,1,000 nm×400 nm discoidal polymeric nanoconstructs(DPN)encapsulating docetaxel(DTXL)and the near infrared compound Iipid-Cy5 were engineered.DPN were obtained by filling multiple times cylindrical wells in a poly(vinyl alcohol)template with a polymer mixture comprising poly(lactic-co-glycolic acid)(PLGA)and poly(ethylene glycol)diacrylate(PEG-DA)chains together with therapeutic and imaging agents.The resulting“multi-passage”DPN exhibited higher DTXL loading,Iipid-Cy5 stability,and stiffness as compared to the conventional"single-passage"approach.Confocal microscopy confirmed that DTXL-DPN were not taken up by MDA-MB-231 cells but would rather sit next to the cell membrane and slowly release DTXL thereof.Empty DPN had no toxicity on TNBC cells,whereas DTXL-DPN presented a cytotoxic potential comparable to free DTXL(IC50=2.6 nM±1.0 nM vs.7.0 nM±1.09 nM at 72 h).In orthotopic murine models,DPN accumulated in TNBC more efficiently than free-DTXL.With only 2 mg/kg DTXL,intravenously administered every 2 days for a total of 13 treatments,DTXL-DPN induced tumor regression and were associated to an overall 80%survival rate as opposed to a 30%survival rate for free-DTXL,at 120 days.All untreated mice succumbed before 90 days.Collectively,this data demonstrates that vascular confined multi-passage DPN,biomimicking the behavior of circulating platelets,can efficiently deliver chemotherapeutic molecules to malignant tissues and effectively treat orthotopic TNBC at minimal taxane doses. 相似文献
995.
John S. Preston Anna C. du Preez 《Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986)》1998,71(1):43-50
The solvent extraction of nickel and calcium from acidic solutions by mixtures of dinonylnaphthalene sulphonic acid (DNNSA) and different pyridinecarboxylate esters (2-, 3- and 4-C5H4.CO.OR, where R = n-octyl, 2-ethylhexyl and 2-octyl) in xylene was investigated. In contrast to extraction systems employing DNNSA alone, these mixtures permit the separation of nickel and calcium to be carried out, especially when an excess of the ester is used. The extractability of base metals from sulphate solutions by mixtures of DNNSA (0·25 M ) and isodecyl 3-pyridinecarboxylate (0·25 M ) in Shellsol K decreases through the series Cu > Ni > Al > Co > Ca > Zn > Fe(III) > Mg. Mixtures containing the 2- or 4-ester showed a slightly different selectivity series: Cu > Ni > Co > Zn > Al > Fe(III) ≥ Ca > Mg. In a batch countercurrent experiment, a simulated leach liquor containing Ni 2·15, Mg 5·05 and Ca 0·42 g dm−3 (initial pH 3·0) was extracted with the mixed reagent (0·25 M DNNSA plus 0·25 M 4-ester) in four stages at unit phase ratio, without any pH adjustment. The recovery of nickel was 91%, with co-extractions of calcium and magnesium of 14 and 8%, respectively. When the concentration of the 4-ester was increased to 0·50 M , the recovery of nickel increased to 95%, whilst the co-extractions of calcium and magnesium decreased to 4 and 3%, respectively. © 1998 SCI. 相似文献
996.
Diamela Carías Anna M Cioccia Patricio Hevia 《Journal of the science of food and agriculture》1998,78(4):479-485
Previous studies have shown that the activities of the hepatic enzymes xanthine dehydrogenase and nucleoside phosphorylase, as well as the uric acid excreted, can be used to determine the quality of the protein consumed in chickens, in a short time and using a small amount of the test protein. A common observation in protein quality evaluation is that the food intake of the control animals is considerably greater than that observed in those receiving proteins of low quality. Since this can affect the results, this study measured the quality of garbanzo bean and black bean proteins in chickens fed these beans ad libitum, feeding the bean diets at the level observed in the controls (soy protein+methionine) by enteral intubation or pair feeding the controls with the amount of food consumed by the chickens receiving the bean diets. In every case, protein quality was determined by protein efficiency ratio, net protein utilisation or the biochemical methods used in this study. The results showed that, when fed ad libitum, the animals assigned to the bean diets exhibited a lower food intake than the controls but, by tube feeding, food intake was made equal in both groups. Equal consumption, between these groups, was also obtained by reducing the amount of food offered to the controls to the levels measured in the groups assigned to the bean diets (pair feeding). These feeding strategies had a marked effect on growth, carcass protein content, protein catabolism and also in the results of protein quality. Thus, the control whose intake was reduced grew less, accumulated less protein in tissues and catabolised more of the protein consumed than the control fed ad libitum. In contrast, the chickens assigned to the bean diets, but whose food intake was increased by tube feeding, grew better, accumulated more protein in tissues and catabolised less protein. In general, the results of these experiments confirm the effectiveness of the biochemical methods for estimating protein quality and indicate that the protein quality of both garbanzo beans and black beans increased when it was measured at a food intake equivalent to that measured in the control animals. Since the overall purpose of this study was to evaluate techniques for protein quality determination meant to be applicable to humans nutrition rather than poultry nutrition, single proteins were used instead of combinations of proteins. © 1998 Society of Chemical Industry. 相似文献
997.
Beln Surez Anna Picinelli Javier Moreno Juan J Mangas 《Journal of the science of food and agriculture》1998,78(4):461-465
An analytical procedure for the quantitative determination of the major polyphenols in apple juices which successfully employs a RP-HPLC system without prior treatment of the sample is described. Apple juices were clarified by microfiltration and ultrafiltration without previous treatment. Polyphenols monitored were influenced by clarification technology employed for stabilising the apple juices. The p-coumaric acid derivative was significantly affected by membrane type and filtration time, while (−)-epicatechin and phloridzin were influenced by filtration time. © 1998 Society of Chemical Industry. 相似文献
998.
Nathalia Müller Mateus Eugenio Luciana F. Romo Jorge Marcondes de Souza Soniza V. AlvesLeon Loraine Campanati Celso SantAnna 《IET nanobiotechnology / IET》2021,15(6):558
Glioblastoma is the most life‐threatening tumour of the central nervous system. Temozolomide (TMZ) is the first‐choice oral drug for the treatment of glioblastoma, although it shows low efficacy. Silver nanoparticles (AgNPs) have been shown to exhibit biocidal activity in a variety of microorganisms, including some pathogenic microorganisms. Herein, the antiproliferative effect of AgCl‐NPs on glioblastoma cell lines (GBM02 and GBM11) and on astrocytes was evaluated through automated quantitative image‐based analysis (HCA) of the cells. The cells were treated with 0.1‐5.0 μg/ml AgCl‐NPs or with 9.7‐48.5 μg/ml TMZ. Cells that received combined treatment were also analysed. At a maximum tested concentration of AgCl‐NPs, GBM02 and GBM11, the growth decreased by 93% and 40%, respectively, following 72 h of treatment. TMZ treatment decreased the proliferation of GBM02 and GBM11 cells by 58% and 34%, respectively. Combinations of AgCl‐NPs and TMZ showed intermediate antiproliferative effects; the lowest concentrations caused an inhibition similar to that obtained with TMZ, and the highest concentrations caused inhibition similar to that obtained with AgCl‐NPs alone. No significant changes in astrocyte proliferation were observed. The authors’ findings showed that HCA is a fast and reliable approach that can be used to evaluate the antiproliferative effect of the nanoparticles at the single‐cell level and that AgCl‐NPs are promising agents for glioblastoma treatment. 相似文献
999.
1000.
Piotr Ciesielski Pawe J
wiak Ewa Forma Anna Krzelak 《International journal of molecular sciences》2021,22(24)
TET3 is a member of the TET (ten-eleven translocation) proteins family that catalyzes the conversion of the 5-methylcytosine into 5-hydroxymethylcytosine. TET proteins can also affect chromatin modifications and gene expression independently of their enzymatic activity via interactions with other proteins. O-GlcNAc transferase (OGT), the enzyme responsible for modification of proteins via binding of N-acetylglucosamine residues, is one of the proteins whose action may be dependent on TET3. Here, we demonstrated that in endometrial cancer cells both TET3 and OGT affected the expression of genes involved in epithelial to mesenchymal transition (EMT), i.e., FOXC1, TWIST1, and ZEB1. OGT overexpression was caused by an increase in TWIST1 and ZEB1 levels in HEC-1A and Ishikawa cells, which was associated with increased O-GlcNAcylation of histone H2B and trimethylation of H3K4. The TET3 had the opposite effect on gene expressions and histone modifications. OGT and TET3 differently affected FOXC1 expression and the migratory potential of HEC-1A and Ishikawa cells. Analysis of gene expressions in cancer tissue samples from endometrial cancer patients confirmed the association between OGT or TET3 and EMT genes. Our results contribute to the knowledge of the role of the TET3/OGT relationship in the complex mechanism supporting endometrial cancer progression. 相似文献