全文获取类型
收费全文 | 9103篇 |
免费 | 919篇 |
国内免费 | 381篇 |
出版年
2023年 | 40篇 |
2022年 | 62篇 |
2021年 | 249篇 |
2020年 | 221篇 |
2019年 | 283篇 |
2018年 | 323篇 |
2017年 | 255篇 |
2016年 | 361篇 |
2015年 | 532篇 |
2014年 | 591篇 |
2013年 | 644篇 |
2012年 | 862篇 |
2011年 | 736篇 |
2010年 | 536篇 |
2009年 | 476篇 |
2008年 | 616篇 |
2007年 | 543篇 |
2006年 | 479篇 |
2005年 | 455篇 |
2004年 | 475篇 |
2003年 | 414篇 |
2002年 | 361篇 |
2001年 | 194篇 |
2000年 | 131篇 |
1999年 | 127篇 |
1998年 | 85篇 |
1997年 | 53篇 |
1996年 | 38篇 |
1995年 | 25篇 |
1994年 | 32篇 |
1993年 | 12篇 |
1992年 | 24篇 |
1991年 | 19篇 |
1990年 | 15篇 |
1989年 | 8篇 |
1988年 | 14篇 |
1987年 | 8篇 |
1986年 | 7篇 |
1985年 | 9篇 |
1983年 | 7篇 |
1982年 | 5篇 |
1979年 | 6篇 |
1978年 | 7篇 |
1976年 | 4篇 |
1975年 | 4篇 |
1974年 | 4篇 |
1973年 | 6篇 |
1970年 | 4篇 |
1969年 | 5篇 |
1967年 | 5篇 |
排序方式: 共有10000条查询结果,搜索用时 140 毫秒
81.
Acetylation changes tau interactome to degrade tau in Alzheimer’s disease animal and organoid models
Heesun Choi Haeng Jun Kim Jinhee Yang Sehyun Chae Wonik Lee Sunwoo Chung Jisoo Kim Hyunjung Choi Hyeseung Song Chang Kon Lee Jae Hyun Jun Yong Jae Lee Kyunghyeon Lee Semi Kim Hye‐ri Sim Young Il Choi Keun Ho Ryu Jong‐Chan Park Dongjoon Lee Sun‐Ho Han Daehee Hwang Jangbeen Kyung Inhee Mook‐Jung 《Aging cell》2020,19(1)
Alzheimer's disease (AD) is an age‐related neurodegenerative disease. The most common pathological hallmarks are amyloid plaques and neurofibrillary tangles in the brain. In the brains of patients with AD, pathological tau is abnormally accumulated causing neuronal loss, synaptic dysfunction, and cognitive decline. We found a histone deacetylase 6 (HDAC6) inhibitor, CKD‐504, changed the tau interactome dramatically to degrade pathological tau not only in AD animal model (ADLPAPT) brains containing both amyloid plaques and neurofibrillary tangles but also in AD patient‐derived brain organoids. Acetylated tau recruited chaperone proteins such as Hsp40, Hsp70, and Hsp110, and this complex bound to novel tau E3 ligases including UBE2O and RNF14. This complex degraded pathological tau through proteasomal pathway. We also identified the responsible acetylation sites on tau. These dramatic tau‐interactome changes may result in tau degradation, leading to the recovery of synaptic pathology and cognitive decline in the ADLPAPT mice. 相似文献
82.
83.
84.
Jin‐Ling Fu Qiong Yu Meng‐Di Li Chun‐Mei Hu Guang Shi 《Journal of biochemical and molecular toxicology》2020,34(5)
Heart failure (HF) is a medical condition inability of the heart to pump sufficient blood to meet the metabolic demand of the body to take place. The number of hospitalized patients with cardiovascular diseases is estimated to be more than 1 million each year, of which 80% to 90% of patients ultimately progress to decompensated HF. Digitalis glycosides exert modest inotropic actions when administered to patients with decompensated HF. Although its efficacy in patients with HF and atrial fibrillation is clear, its value in patients with HF and sinus rhythm has often been questioned. A series of recent studies have cast serious doubt on the benefit of digoxin when added to contemporary HF treatment. We are hypothesizing the role and mechanism of exosome and its biological constituents responsible for worsening the disease state and mortality in decompensated HF patients on digitalis. 相似文献
85.
Xiao‐Li Li Fei Yu Bao‐Ying Li Chun‐Li Fu Xin Yu Mei Xu Mei Cheng Hai‐Qing Gao 《Cell biology international》2020,44(1):268-277
The progression of diabetic cardiomyopathy is related to cardiomyocyte dysfunction and apoptosis. Our previous studies showed that asporin (ASPN) was significantly increased in the myocardium of db/db mice through proteomics, and grape seed procyanidin B2 (GSPB2) significantly inhibited the expression of ASPN in the heart of db/db mice. We report here that ASPN played a critical role in glycated low‐density lipoproteins (gly‐LDL) induced‐cardiomyocyte apoptosis. We found that gly‐LDL upregulated ASPN expression. ASPN increased H9C2 cardiomyocyte apoptosis with down‐regulation of Bcl‐2, upregulation of transforming growth factor‐β1, Bax, collagen III, fibronectin, and phosphorylation of smad2 and smad3. However, GSPB2 treatment reversed ASPN‐induced impairments in H9C2 cardiomyocytes. These results provide evidence for the cardioprotective action of GSPB2 against ASPN injury, and thus suggest a new target for fighting against diabetic cardiomyopathy. 相似文献
86.
Mi Hye Kim Jae Yeop Kim Jung‐Hak Kim Hyun‐Shik Lee Jae‐Won Huh Dong‐Seok Lee 《Cell biology international》2020,44(10):2086-2093
Reactive oxygen species (ROS) act as signaling molecules to regulate various cell functions. Numerous studies have demonstrated ROS to be essential for the differentiation of adipocytes. Peroxiredoxins (Prxs) are a ubiquitous family of antioxidant enzymes in mammalian cells. Prx2 is present in the cytoplasm and cell membranes and demonstrates ROS scavenging activity. We focused on Prx2 involvement in regulating adipogenesis and lipid accumulation and demonstrated that Prx2 expression was upregulated during adipocyte differentiation. In addition, the silencing of Prx2 (shPrx2) inhibited adipogenesis by modulating adipogenic gene expression, and cell death was enhanced via increased ROS production in shPrx2‐3T3‐L1 cells. These results demonstrate that shPrx2 triggers adipocyte cell death and weakens adipocyte function via ROS production. Taken together, our data suggest the participation of Prx2 in adipocyte function and differentiation. Our results also imply that the downregulation of Prx2 activity could help prevent obesity. Overall, findings support the development of ROS‐based therapeutic solutions for the treatment of obesity and obesity‐related metabolic disorders. 相似文献
87.
Scyllo‐inositol (SI), a stereoisomer of inositol, is regarded as a promising therapeutic agent for Alzheimer's disease. Here, an in vitro cofactor‐balance biotransformation for the production of SI from myo‐inositol (MI) by thermophilic myo‐inositol 2‐dehydrogenase (IDH) and scyllo‐inositol 2‐dehydrogenase (SIDH) is presented. These two enzymes (i.e., IDH and SIDH from Geobacillus kaustophilus) are co‐expressed in Escherichia coli BL21(DE3), and E. coli cells containing the two enzymes are permeabilized by heat treatment as whole‐cell catalysts to convert MI to SI. After condition optimizations about permeabilized temperature, reaction temperature, and initial MI concentration, about 82 g L?1 of SI is produced from 250 g L?1 of MI within 24 h without any cofactor supplementation. This final titer of SI produced is the highest to the authors’ limited knowledge. This study provides a promising method for the large‐scale industrial production of SI. 相似文献
88.
89.
Ra Mi Woo Min Gu Park Jae Young Choi Dong Hwan Park Jun Young Kim Minghui Wang Hyun Ji Kim Soo Dong Woo Jae Su Kim Yeon Ho Je 《Journal of Applied Entomology》2020,144(7):655-663
Insect growth regulators (IGRs) are effective alternatives to chemical insecticides because of their specificity and low environmental toxicity. Entomopathogenic fungi are an important natural pathogen of insects and have been developed as biological control agents. They produce a wide range of secondary metabolites such as antibiotics, pesticides, growth-promoting or inhibiting compounds and insect attracting agents. In this study, to explore novel IGR substances from entomopathogenic fungi, culture extracts of 189 entomopathogenic fungi isolated from Korean soil samples were investigated for their juvenile hormone (JH)-based IGR activities. Whereas none of the culture extracts exhibited JH agonist (JHA) activity, 14 extracts showed high levels of JH antagonist (JHAN) activity. Among them, culture extract of JEF-145 strain, which was identified as Lecanicillium attenuatum, showed the highest insecticidal against Aedes albopictus and Plutella xylostella. At liquid culture condition, JHAN activity was observed in culture soup rather than mycelial cake, indicating that substances with JHAN activity are released from the JEF-145 strain during culture. Furthermore, while extract from solid cultured JEF-145 strain showed insecticidal activities against both A. albopictus and P. xylostella, that from liquid cultured fungi showed insecticidal activity only against A. albopictus, indicating that L. attenuatum JEF-145 strain produces different kinds of secondary metabolites with JHAN activity depending on culture conditions. These results suggested that JHAN substances derived from entomopathogenic fungi could be usefully exploited to develop novel eco-friendly IGR insecticides. 相似文献
90.