全文获取类型
收费全文 | 819篇 |
免费 | 67篇 |
国内免费 | 4篇 |
学科分类
工业技术 | 890篇 |
出版年
2024年 | 14篇 |
2023年 | 24篇 |
2022年 | 133篇 |
2021年 | 120篇 |
2020年 | 41篇 |
2019年 | 49篇 |
2018年 | 50篇 |
2017年 | 34篇 |
2016年 | 42篇 |
2015年 | 52篇 |
2014年 | 31篇 |
2013年 | 53篇 |
2012年 | 40篇 |
2011年 | 41篇 |
2010年 | 27篇 |
2009年 | 18篇 |
2008年 | 10篇 |
2007年 | 20篇 |
2006年 | 12篇 |
2005年 | 19篇 |
2004年 | 14篇 |
2003年 | 6篇 |
2002年 | 6篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 4篇 |
1997年 | 1篇 |
1996年 | 4篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1991年 | 3篇 |
1989年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
排序方式: 共有890条查询结果,搜索用时 15 毫秒
1.
Total superoxide dismutase (SOD:superoxide: superoxide oxidoreductase; EC 1.15.1.1) activity and individual activities of its three different metalloenzymes, CuZn-SOD, Fe-SOD, and Mn-SOD, were investigated during senescence of apples (Malus domestica Borkh.). Total SOD activity and relative activities of its three forms varied greatly among cultivars. Activities underwent considerable change during senescence of fruit, but changes were different among cultivars. Whether fruit senesced at 0°C or 20°C had little effect on SOD activities, and application of the antioxidant diphenylamine (DPA) did not alter activities. SOD activities increased with occurrence of the physiological disorder “senescent breakdown,” but did not increase with occurrence of the disorder “superficial scald.” In a given apple cultivar, changes in total SOD activity generally paralleled activities of the different SOD forms. Such activity may reflect changes affecting food and nutritive quality of the fruit. 相似文献
2.
A decay of fresh-cut celery (Apium graveolens) segments stored at < 5°C in sealed film bags began with a water soaking of the cut surfaces. Slimy moisture accumulated inside the bags. The segments water soaked completely, softened, discolored and sometimes disintegrated. Total aerobic bacterial populations isolated from decayed segments ranged from log10 7.0–7.7 CFU/g tissue weight. The predominant bacteria, identified by fatty acid analysis as Pseudomonas fluorescens and P. marginalis, caused water soaking, soft rot, and discoloration in freshly inoculated celery tissues stored at 5 or 25°C. Leuconostoc mesenteroides was also isolated and may have been responsible for slime production. 相似文献
3.
4.
Rocío Mato-Basalo Miriam Morente-Lpez Onno J Arntz Fons A. J. van de Loo Juan Fafin-Labora María C. Arufe 《International journal of molecular sciences》2021,22(7)
Mesenchymal stem cells have an important potential in the treatment of age-related diseases. In the last years, small extracellular vesicles derived from these stem cells have been proposed as cell-free therapies. Cellular senescence and proinflammatory activation are involved in the loss of therapeutic capacity and in the phenomenon called inflamm-aging. The regulators of these two biological processes in mesenchymal stem cells are not well-known. In this study, we found that p65 is activated during cellular senescence and inflammatory activation in human umbilical cord-derived mesenchymal stem cell. To demonstrate the central role of p65 in these two processes, we used small-molecular inhibitors of p65, such as JSH-23, MG-132 and curcumin. We found that the inhibition of p65 prevents the cellular senescence phenotype in human umbilical cord-derived mesenchymal stem cells. Besides, p65 inhibition produced the inactivation of proinflammatory molecules as components of a senescence-associated secretory phenotype (SASP) (interleukin-6 and interleukin-8 (IL-6 and IL-8)). Additionally, we found that the inhibition of p65 prevents the transmission of paracrine senescence between mesenchymal stem cells and the proinflammatory message through small extracellular vesicles. Our work highlights the important role of p65 and its inhibition to restore the loss of functionality of small extracellular vesicles from senescent mesenchymal stem cells and their inflamm-aging signature. 相似文献
5.
Fiqri D. Khaidizar Yasumasa Bessho Yasukazu Nakahata 《International journal of molecular sciences》2021,22(7)
Aging is a phenomenon underlined by complex molecular and biochemical changes that occur over time. One of the metabolites that is gaining strong research interest is nicotinamide adenine dinucleotide, NAD+, whose cellular level has been shown to decrease with age in various tissues of model animals and humans. Administration of NAD+ precursors, nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), to supplement NAD+ production through the NAD+ salvage pathway has been demonstrated to slow down aging processes in mice. Therefore, NAD+ is a critical metabolite now understood to mitigate age-related tissue function decline and prevent age-related diseases in aging animals. In human clinical trials, administration of NAD+ precursors to the elderly is being used to address systemic age-associated physiological decline. Among NAD+ biosynthesis pathways in mammals, the NAD+ salvage pathway is the dominant pathway in most of tissues, and NAMPT is the rate limiting enzyme of this pathway. However, only a few activators of NAMPT, which are supposed to increase NAD+, have been developed so far. In this review, we will focus on the importance of NAD+ and the possible application of an activator of NAMPT to promote successive aging. 相似文献
6.
Tanyalak Parimon Miriam S. Hohmann Changfu Yao 《International journal of molecular sciences》2021,22(12)
Pulmonary fibrosis is a chronic and fatal lung disease that significantly impacts the aging population globally. To date, anti-fibrotic, immunosuppressive, and other adjunct therapy demonstrate limited efficacies. Advancing our understanding of the pathogenic mechanisms of lung fibrosis will provide a future path for the cure. Cellular senescence has gained substantial interest in recent decades due to the increased incidence of fibroproliferative lung diseases in the older age group. Furthermore, the pathologic state of cellular senescence that includes maladaptive tissue repair, decreased regeneration, and chronic inflammation resembles key features of progressive lung fibrosis. This review describes regulatory pathways of cellular senescence and discusses the current knowledge on the senescence of critical cellular players of lung fibrosis, including epithelial cells (alveolar type 2 cells, basal cells, etc.), fibroblasts, and immune cells, their phenotypic changes, and the cellular and molecular mechanisms by which these cells contribute to the pathogenesis of pulmonary fibrosis. A few challenges in the field include establishing appropriate in vivo experimental models and identifying senescence-targeted signaling molecules and specific therapies to target senescent cells, known collectively as “senolytic” or “senotherapeutic” agents. 相似文献
7.
The effect and the action mechanism of lanthanum on GF43 plantlet in vitro were studied. The results of experiments show that root growth rate and dry weight of GF43 by LaCI3 treatments increase. The activities of antioxidant enzymes in root system such as superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) apparently enhance. Moreover O^-2 and malond ialdehyde (MDA) contents and cell membrane permeability of GF43 are decreased by LaC13. The relatively stable membrane structure of cell could also be maintained and the root ageing of GF43 plantlet in vitro delays. 相似文献
8.
Huan Wang Yanan Sun Chenchen Pi Xiao Yu Xingyu Gao Chang Zhang Hui Sun Haiying Zhang Yingai Shi Xu He 《International journal of molecular sciences》2022,23(23)
In vitro expansion-mediated replicative senescence has severely limited the clinical applications of mesenchymal stem cells (MSCs). Accumulating studies manifested that nicotinamide adenine dinucleotide (NAD+) depletion is closely related to stem cell senescence and mitochondrial metabolism disorder. Promoting NAD+ level is considered as an effective way to delay aging. Previously, we have confirmed that nicotinamide mononucleotide (NMN), a precursor of NAD+, can alleviate NAD+ deficiency-induced MSC senescence. However, whether NMN can attenuate MSC senescence and its underlying mechanisms are still incompletely clear. The present study herein showed that late passage (LP) MSCs displayed lower NAD+ content, reduced Sirt3 expression and mitochondrial dysfunction. NMN supplementation leads to significant increase in intracellular NAD+ level, NAD+/ NADH ratio, Sirt3 expression, as well as ameliorated mitochondrial function and rescued senescent MSCs. Additionally, Sirt3 over-expression relieved mitochondrial dysfunction, and retrieved senescence-associated phenotypic features in LP MSCs. Conversely, inhibition of Sirt3 activity via a selective Sirt3 inhibitor 3-TYP in early passage (EP) MSCs resulted in aggravated cellular senescence and abnormal mitochondrial function. Furthermore, NMN administration also improves 3-TYP-induced disordered mitochondrial function and cellular senescence in EP MSCs. Collectively, NMN replenishment alleviates mitochondrial dysfunction and rescues MSC senescence through mediating NAD+/Sirt3 pathway, possibly providing a novel mechanism for MSC senescence and a promising strategy for anti-aging pharmaceuticals. 相似文献
9.
Liqiang Qiu Xiaoxiong Liu Hao Xia Changwu Xu 《International journal of molecular sciences》2022,23(20)
Increasing evidence has shown that vascular aging has a key role in the pathogenesis of vascular diseases. P300/CBP-associated factor (PCAF) is involved in many vascular pathological processes, but the role of PCAF in vascular aging is unknown. This study aims to explore the role and underlying mechanism of PCAF in vascular aging. The results demonstrated that the expression of PCAF was associated with age and aging, and remarkably increased expression of PCAF was present in human atherosclerotic coronary artery. Downregulation of PCAF could reduce angiotensin II (AngII)-induced senescence of rat aortic endothelial cells (ECs) in vitro. In addition, inhibition of PCAF with garcinol alleviated AngII-induced vascular senescence phenotype in mice. Downregulation of PCAF could alleviate AngII-induced oxidative stress injury in ECs and vascular tissue. Moreover, PCAF and nuclear factor erythroid-2-related factor 2 (Nrf2) could interact directly, and downregulation of PCAF alleviated vascular aging by promoting the activation of Nrf2 and enhancing the expression of its downstream anti-aging factors. The silencing of Nrf2 with small interfering RNA attenuated the protective effect of PCAF downregulation from vascular aging. These findings indicate that downregulation of PCAF alleviates oxidative stress by activating the Nrf2 signaling pathway and ultimately inhibits vascular aging. Thus, PCAF may be a promising target for aging-related cardiovascular disease. 相似文献
10.
Ahyeon Jeong Yena Cho Minkyeong Cho Gyu-Un Bae Dae-Geun Song Su-Nam Kim Yong Kee Kim 《International journal of molecular sciences》2022,23(20)
Protein arginine methyltransferase 7 (PRMT7) regulates various cellular responses, including gene expression, cell migration, stress responses, and stemness. In this study, we investigated the biological role of PRMT7 in cell cycle progression and DNA damage response (DDR) by inhibiting PRMT7 activity with either SGC8158 treatment or its specific siRNA transfection. Suppression of PRMT7 caused cell cycle arrest at the G1 phase, resulting from the stabilization and subsequent accumulation of p21 protein. In addition, PRMT7 activity is closely associated with DNA repair pathways, including both homologous recombination and non-homologous end-joining. Interestingly, SGC8158, in combination with doxorubicin, led to a synergistic increase in both DNA damage and cytotoxicity in MCF7 cells. Taken together, our data demonstrate that PRMT7 is a critical modulator of cell growth and DDR, indicating that it is a promising target for cancer treatment. 相似文献