全文获取类型
| 收费全文 | 280篇 |
| 免费 | 19篇 |
| 国内免费 | 8篇 |
专业分类
| 电工技术 | 1篇 |
| 综合类 | 5篇 |
| 化学工业 | 176篇 |
| 金属工艺 | 10篇 |
| 机械仪表 | 15篇 |
| 建筑科学 | 5篇 |
| 轻工业 | 37篇 |
| 水利工程 | 2篇 |
| 无线电 | 13篇 |
| 一般工业技术 | 35篇 |
| 冶金工业 | 3篇 |
| 原子能技术 | 4篇 |
| 自动化技术 | 1篇 |
出版年
| 2025年 | 1篇 |
| 2024年 | 4篇 |
| 2023年 | 5篇 |
| 2022年 | 54篇 |
| 2021年 | 59篇 |
| 2020年 | 12篇 |
| 2019年 | 11篇 |
| 2018年 | 8篇 |
| 2017年 | 8篇 |
| 2016年 | 9篇 |
| 2015年 | 10篇 |
| 2014年 | 13篇 |
| 2013年 | 15篇 |
| 2012年 | 11篇 |
| 2011年 | 7篇 |
| 2010年 | 7篇 |
| 2009年 | 6篇 |
| 2008年 | 10篇 |
| 2007年 | 3篇 |
| 2006年 | 10篇 |
| 2005年 | 8篇 |
| 2004年 | 9篇 |
| 2003年 | 2篇 |
| 2002年 | 8篇 |
| 2001年 | 3篇 |
| 2000年 | 2篇 |
| 1999年 | 4篇 |
| 1997年 | 2篇 |
| 1995年 | 2篇 |
| 1991年 | 2篇 |
| 1982年 | 1篇 |
| 1971年 | 1篇 |
排序方式： 共有307条查询结果，搜索用时 15 毫秒
71.
Szu-Kai Chen Chu-Hsi Hsu Min-Lang Tsai Rong-Huei Chen Gregor P. C. Drummen 《International journal of molecular sciences》2013,14(10):19399-19415
The aim of this study was to evaluate the in cellulo inhibition of hydrogen-peroxide-induced oxidative stress in skin fibroblasts using different low-molecular-weight polysaccharides (LMPS) prepared from agar (LMAG), chitosan (LMCH) and starch (LMST), which contain various different functional groups (i.e., sulfate, amine, and hydroxyl groups). The following parameters were evaluated: cell viability, intracellular oxidant production, lipid peroxidation, and DNA damage. Trolox was used as a positive control in order to allow comparison of the antioxidant efficacies of the various LMPS. The experimentally determined attenuation of oxidative stress by LMPS in skin fibroblasts was: LMCH > LMAG > LMST. The different protection levels of these LMPS may be due to the physic-chemical properties of the LMPS’ functional groups, including electron transfer ability, metal ion chelating capacities, radical stabilizing capacity, and the hydrophobicity of the constituent sugars. The results suggest that LMCH might constitute a novel and potential dermal therapeutic and sun-protective agent. 相似文献
72.
目的 探讨成纤维细胞生长因子21(FGF21)促进泡沫细胞胆固醇流出的机制。方法 在建立THP-1巨噬细胞源性泡沫细胞模型的基础上,以不同浓度(0、50、100、200、400 μg/L)FGF21处理泡沫细胞24 h,以200 μg/L FGF21处理泡沫细胞不同时间(0、6、12、24、48 h),Western blot、激光共聚焦检测LC3,MDC染色分析自噬小体,HPLC、油红O染色测定细胞内胆固醇蓄积,液体闪烁计数分析胆固醇流出。结果 200、400 μg/L的FGF21,以及200 μg/L的FGF21作用24 h和48 h,泡沫细胞总胆固醇(TC)、游离胆固醇(FC)和胆固醇酯(CE)水平均显著降低,而其胆固醇流出显著增强。机制研究发现,FGF21可诱导泡沫细胞自噬体形成,且微管相关蛋白Ⅰ轻链3(LC3-Ⅰ)至微管相关蛋白Ⅱ轻链3(LC3-Ⅱ)转化率显著增加,但自噬相关基因5(ATG5)siRNA或3-甲基腺嘌呤(3-MA)或巴弗洛霉素A1(BafA1)干预自噬后,FGF21对TC、FC和CE的降低作用减弱,同时胆固醇流出减少,泡沫细胞脂质蓄积加重。结论 FGF21通过上调自噬促进泡沫细胞胆固醇流出。 相似文献
73.
74.
The normal dermal human fibroblastic cell (NDHF) was used to determine a cellular ageing pattern. Cells were cultured in monolayers until the 30th passage. First of all, the following cell growth characteristics were studied: growth rate, fluorimetric DNA determination, DNA repair after UV irradiation. Secondly, metabolism characteristics were examined: lysosomal enzymatic activity and type I and III collagen biosynthesis. Strains were obtained from 10,30,43 and 69-year-old donors to favour a comparison between in vitro and in vivo ageing.
Cell growth ability is modified in vitro only for the oldest strain which shows a significant decrease in the cellular density at the 30th passage. The DNA rate and its repairing ability are not changed by in vitro ageing whatever the strain age.
Lysosomal activity increases during in vitro ageing whereas the collagen I synthesis decreases.
In vitro proliferating potentialities do not reflect in vivo ageing. On the other hand, in this study, metabolic potentialities evolve in the same way in vitro as in vivo and could be a good enough pattern to select anti-ageing products. 相似文献
Cell growth ability is modified in vitro only for the oldest strain which shows a significant decrease in the cellular density at the 30th passage. The DNA rate and its repairing ability are not changed by in vitro ageing whatever the strain age.
Lysosomal activity increases during in vitro ageing whereas the collagen I synthesis decreases.
In vitro proliferating potentialities do not reflect in vivo ageing. On the other hand, in this study, metabolic potentialities evolve in the same way in vitro as in vivo and could be a good enough pattern to select anti-ageing products. 相似文献
75.
76.
Irene Reimche Haiqian Yu Ni Putu Ariantari Zhen Liu Kay Merkens Stella Rotfuß Karin Peter Ute Jungwirth Nadine Bauer Friedemann Kiefer Jrg-Martin Neudrfl Hans-Günther Schmalz Peter Proksch Nicole Teusch 《International journal of molecular sciences》2022,23(18)
Triple-negative breast cancer (TNBC), representing the most aggressive form of breast cancer with currently no targeted therapy available, is characterized by an inflammatory and hypoxic tumor microenvironment. To date, a broad spectrum of anti-tumor activities has been reported for phenanthroindolizidine alkaloids (PAs), however, their mode of action in TNBC remains elusive. Thus, we investigated six naturally occurring PAs extracted from the plant Tylophora ovata: O-methyltylophorinidine (1) and its five derivatives tylophorinidine (2), tylophoridicine E (3), 2-demethoxytylophorine (4), tylophoridicine D (5), and anhydrodehydrotylophorinidine (6). In comparison to natural (1) and for more-in depth studies, we also utilized a sample of synthetic O-methyltylophorinidine (1s). Our results indicate a remarkably effective blockade of nuclear factor kappa B (NFκB) within 2 h for compounds (1) and (1s) (IC50 = 17.1 ± 2.0 nM and 3.3 ± 0.2 nM) that is different from its effect on cell viability within 24 h (IC50 = 13.6 ± 0.4 nM and 4.2 ± 1 nM). Furthermore, NFκB inhibition data for the additional five analogues indicate a structure–activity relationship (SAR). Mechanistically, NFκB is significantly blocked through the stabilization of its inhibitor protein kappa B alpha (IκBα) under normoxic as well as hypoxic conditions. To better mimic the TNBC microenvironment in vitro, we established a 3D co-culture by combining the human TNBC cell line MDA-MB-231 with primary murine cancer-associated fibroblasts (CAF) and type I collagen. Compound (1) demonstrates superiority against the therapeutic gold standard paclitaxel by diminishing spheroid growth by 40% at 100 nM. The anti-proliferative effect of (1s) is distinct from paclitaxel in that it arrests the cell cycle at the G0/G1 state, thereby mediating a time-dependent delay in cell cycle progression. Furthermore, (1s) inhibited invasion of TNBC monoculture spheroids into a matrigel®-based environment at 10 nM. In conclusion, PAs serve as promising agents with presumably multiple target sites to combat inflammatory and hypoxia-driven cancer, such as TNBC, with a different mode of action than the currently applied chemotherapeutic drugs. 相似文献
77.
Thanachai Methatham Ryozo Nagai Kenichi Aizawa 《International journal of molecular sciences》2022,23(8)
The accumulation of fibrosis in cardiac tissues is one of the leading causes of heart failure. The principal cellular effectors in cardiac fibrosis are activated fibroblasts and myofibroblasts, which serve as the primary source of matrix proteins. TGF-β signaling pathways play a prominent role in cardiac fibrosis. The control of TGF-β by KLF5 in cardiac fibrosis has been demonstrated for modulating cardiovascular remodeling. Since the expression of KLF5 is reduced, the accumulation of fibrosis diminishes. Because the molecular mechanism of fibrosis is still being explored, there are currently few options for effectively reducing or reversing it. Studying metabolic alterations is considered an essential process that supports the explanation of fibrosis in a variety of organs and especially the glycolysis alteration in the heart. However, the interplay among the main factors involved in fibrosis pathogenesis, namely TGF-β, KLF5, and the metabolic process in glycolysis, is still indistinct. In this review, we explain what we know about cardiac fibroblasts and how they could help with heart repair. Moreover, we hypothesize and summarize the knowledge trend on the molecular mechanism of TGF-β, KLF5, the role of the glycolysis pathway in fibrosis, and present the future therapy of cardiac fibrosis. These studies may target therapies that could become important strategies for fibrosis reduction in the future. 相似文献
78.
Ting-Wei Lee Cheng-Chih Chung Ting-I Lee Yung-Kuo Lin Yu-Hsun Kao Yi-Jen Chen 《International journal of molecular sciences》2022,23(1)
Fibroblast growth factor (FGF)-23 induces hypertrophy and calcium (Ca2+) dysregulation in cardiomyocytes, leading to cardiac arrhythmia and heart failure. However, knowledge regarding the effects of FGF-23 on cardiac fibrogenesis remains limited. This study investigated whether FGF-23 modulates cardiac fibroblast activity and explored its underlying mechanisms. We performed MTS analysis, 5-ethynyl-2′-deoxyuridine assay, and wound-healing assay in cultured human atrial fibroblasts without and with FGF-23 (1, 5 and 25 ng/mL for 48 h) to analyze cell proliferation and migration. We found that FGF-23 (25 ng/mL, but not 1 or 5 ng/mL) increased proliferative and migratory abilities of human atrial fibroblasts. Compared to control cells, FGF-23 (25 ng/mL)-treated fibroblasts had a significantly higher Ca2+ entry and intracellular inositol 1,4,5-trisphosphate (IP3) level (assessed by fura-2 ratiometric Ca2+ imaging and enzyme-linked immunosorbent assay). Western blot analysis showed that FGF-23 (25 ng/mL)-treated cardiac fibroblasts had higher expression levels of calcium release-activated calcium channel protein 1 (Orai1) and transient receptor potential canonical (TRPC) 1 channel, but similar expression levels of α-smooth muscle actin, collagen type IA1, collagen type Ⅲ, stromal interaction molecule 1, TRPC 3, TRPC6 and phosphorylated-calcium/calmodulin-dependent protein kinase II when compared with control fibroblasts. In the presence of ethylene glycol tetra-acetic acid (a free Ca2+ chelator, 1 mM) or U73122 (an inhibitor of phospholipase C, 1 μM), control and FGF-23-treated fibroblasts exhibited similar proliferative and migratory abilities. Moreover, polymerase chain reaction analysis revealed that atrial fibroblasts abundantly expressed FGF receptor 1 but lacked expressions of FGF receptors 2-4. FGF-23 significantly increased the phosphorylation of FGF receptor 1. Treatment with PD166866 (an antagonist of FGF receptor 1, 1 μM) attenuated the effects of FGF-23 on cardiac fibroblast activity. In conclusion, FGF-23 may activate FGF receptor 1 and subsequently phospholipase C/IP3 signaling pathway, leading to an upregulation of Orai1 and/or TRPC1-mediated Ca2+ entry and thus enhancing human atrial fibroblast activity. 相似文献
79.
Ju-Sheng Shieh Yu-Tang Chin Hsien-Chung Chiu Ya-Yu Hsieh Hui-Rong Cheng Hai Gu Fung-Wei Chang 《International journal of molecular sciences》2022,23(23)
Mesenchymal stem cell (MSC)-derived extracellular vesicles (exosomes) possess regeneration, cell proliferation, wound healing, and anti-senescence capabilities. The functions of exosomes can be modified by preconditioning MSCs through treatment with bio-pulsed reagents (Polygonum multiflorum Thunb extract). However, the beneficial effects of bio-pulsed small extracellular vesicles (sEVs) on the skin or hair remain unknown. This study investigated the in vitro mechanistic basis through which bio-pulsed sEVs enhance the bioactivity of the skin fibroblasts and hair follicle cells. Avian-derived MSCs (AMSCs) were isolated, characterized, and bio-pulsed to produce AMSC-sEVs, which were isolated, lyophilized, characterized, and analyzed. The effects of bio-pulsed AMSC-sEVs on cell proliferation, wound healing, and gene expression associated with skin and hair bioactivity were examined using human skin fibroblasts (HSFs) and follicle dermal papilla cells (HFDPCs). Bio-pulsed treatment significantly enhanced sEVs production by possibly upregulating RAB27A expression in AMSCs. Bio-pulsed AMSC-sEVs contained more exosomal proteins and RNAs than the control. Bio-pulsed AMSC-sEVs significantly augmented cell proliferation, wound healing, and gene expression in HSFs and HFDPCs. The present study investigated the role of bio-pulsed AMSC-sEVs in the bioactivity of the skin fibroblasts and hair follicle cells as mediators to offer potential health benefits for skin and hair. 相似文献
80.
Lúcia Fadiga Mariana Lavrador Nuno Vicente Luísa Barros Catarina I. Gonalves Asma Al-Naama Luis R. Saraiva Manuel C. Lemos 《International journal of molecular sciences》2022,23(8)
Congenital hypogonadotropic hypogonadism (CHH) is a rare reproductive endocrine disorder characterized by complete or partial failure of pubertal development and infertility due to deficiency of the gonadotropin-releasing hormone (GnRH). CHH has a significant clinical heterogeneity and can be caused by mutations in over 30 genes. The aim of this study was to investigate the genetic defect in two siblings with CHH. A woman with CHH associated with anosmia and her brother with normosmic CHH were investigated by whole exome sequencing. The genetic studies revealed a novel heterozygous missense mutation in the Fibroblast Growth Factor Receptor 1 (FGFR1) gene (NM_023110.3: c.242T>C, p.Ile81Thr) in the affected siblings and in their unaffected father. The mutation affected a conserved amino acid within the first Ig-like domain (D1) of the protein, was predicted to be pathogenic by structure and sequence-based prediction methods, and was absent in ethnically matched controls. These were consistent with a critical role for the identified missense mutation in the activity of the FGFR1 protein. In conclusion, our identification of a novel missense mutation of the FGFR1 gene associated with a variable expression and incomplete penetrance of CHH extends the known mutational spectrum of this gene and may contribute to the understanding of the pathogenesis of CHH. 相似文献