全文获取类型
收费全文 | 2228篇 |
免费 | 188篇 |
国内免费 | 137篇 |
专业分类
2553篇 |
出版年
2024年 | 8篇 |
2023年 | 27篇 |
2022年 | 73篇 |
2021年 | 127篇 |
2020年 | 72篇 |
2019年 | 77篇 |
2018年 | 91篇 |
2017年 | 75篇 |
2016年 | 95篇 |
2015年 | 156篇 |
2014年 | 154篇 |
2013年 | 177篇 |
2012年 | 208篇 |
2011年 | 202篇 |
2010年 | 110篇 |
2009年 | 93篇 |
2008年 | 105篇 |
2007年 | 85篇 |
2006年 | 71篇 |
2005年 | 56篇 |
2004年 | 41篇 |
2003年 | 43篇 |
2002年 | 47篇 |
2001年 | 33篇 |
2000年 | 34篇 |
1999年 | 45篇 |
1998年 | 15篇 |
1997年 | 22篇 |
1996年 | 15篇 |
1995年 | 12篇 |
1994年 | 9篇 |
1993年 | 9篇 |
1992年 | 12篇 |
1991年 | 15篇 |
1990年 | 19篇 |
1989年 | 9篇 |
1987年 | 9篇 |
1986年 | 5篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1981年 | 4篇 |
1980年 | 6篇 |
1979年 | 12篇 |
1978年 | 9篇 |
1977年 | 8篇 |
1976年 | 5篇 |
1975年 | 9篇 |
1974年 | 6篇 |
1973年 | 3篇 |
1970年 | 5篇 |
排序方式: 共有2553条查询结果,搜索用时 15 毫秒
81.
82.
Summary Kadazans, the largest indigenous group in Sabah, northern Borneo, were surveyed for glyoxalase I, phosphoglucomutase I, red cell acid phosphatase, esterase D, adenosine deaminase, soluble glutamate pyruvate transaminase, soluble glutamate oxaloacetate transaminase, 6-phosphogluconate dehydrogenase, uridine monophosphate kinase, adenylate kinase, peptidase B and D, superoxide dismutase, C5, group specific component, haptoglobin and transferrin.Kadazans were found to be polymorphic for GLOI, PGMI, RCAP, esterase D, ADA, s-Gpt, 6PGD, UMPK, Gc, C5, haptoglobin and peptidase B. Rare variants were found for transferrin and peptidase D. No variant was found for s-Got, SOD and AK. 相似文献
83.
Hongyu Quan Teng Ma Xianxian Zhao Baixiong Zhao Yunlai Liu Hongli Li 《Cellular and molecular neurobiology》2014,34(4):619-630
The aim of this study was to explore the direct embryonic teratogenicity of vinyl chloride monomer (VCM), especially the toxic effects on the early development of the nervous system and its underlying mechanisms. Pregnant mice at embryonic day 6.5 (E6.5) were injected with different doses of VCM (200, 400 and 600 mg/kg) and embryos were harvested at E10.5. Our results showed that doses higher than 400 mg/kg of VCM increased the incidence of malformed embryos, especially the neural tube defects (NTDs). In addition, high-dose of VCM decreased mitotic figure counts in the neuroepithelium and enhanced the percentage of cells in G0/G1 phase, while they were reduced in S phase. The more VCM was injected into mice, the fewer positive PCNA cells were seen and the more positive TUNEL cells were observed in the neuroepithelium. Moreover, significant increases in the levels of caspase-3 protein were observed in NTD embryos. Our results demonstrate that during early pregnancy, exposure to doses higher than 400 mg/kg of VCM increases the incidence of malformations and particularly the rate of NTDs. High-dose of VCM inhibits the proliferation of neural cells and induces cell apoptosis, leading to an imbalance in the ratio of proliferation and apoptosis. Meanwhile, the apoptosis of neuroepithelial cells might be accelerated by the activation of the caspase-3 pathway, and it might be a reason for NTDs. 相似文献
84.
85.
胆汁是由肝细胞分泌的胆道内的消化液,为等渗溶液,主要成分包括胆盐、胆汁酸、胆红素、还原型谷胱甘肽及其结合物、氧化型谷胱甘肽等。在消化期,胆汁可由肝脏和胆囊大量排到十二指肠,将脂肪乳化成微滴以利于消化;还能促进脂肪酸及脂溶性维生素的吸收。生理状态下胆汁不会反流入胃及食管,也不会损伤肠道。病理状态下胆汁会反流入胃甚至反流到食管损伤胃及食管黏膜,在一些情况下胆汁甚至会损伤肠道的黏膜。目前认为胆汁是较明确的致癌因素,与消化道肿瘤的相关性较大,但仍缺乏针对性的防治方案。明确胆汁对消化道黏膜的损伤机制,有助探索消化道肿瘤防治的新靶点。本文回顾了近年来有关胆汁对食管黏膜、胃黏膜及肠黏膜损伤机制的研究进展,以期为进一步的研究提供思路。 相似文献
86.
Ze Yu Hao Wang Yilin Fang Liangliang Lu Minghao Li Bingru Yan Yuzhe Nie Chunbo Teng 《Journal of cellular biochemistry》2020,121(3):2318-2329
Heat shock proteins (HSPs) were known as the molecular chaperones, which play a pivotal role in the protein quality control system, ensuring correct folding of proteins, and facilitating the correct refolding of damaged proteins via the transient interaction with their substrate proteins. They also practice in the regulation of cell cycles and are involved in apoptosis. We found that HspB2 was almost completely silent in pancreatic cancer and few studies investigated the role of HspB2 in cancer cells, particularly in pancreatic cancer. Here, we reported that HspB2 effectively inhibited cell proliferation in Panc-1 cells. Specifically, we demonstrated that HspB2 could combine mut-p53 and change the DNA binding site of mutant p53, subsequently upregulated the expression of RPRM, BAI-1, and TSAP6 which were the downstream genes of wt-p53, participate in mediating downstream responses to p53, including inhibiting cell proliferation and angiogenesis. The main aim of this study is to investigate the relationship between HspB2 and p53, and provide a novel treatment strategy for pancreatic cancer. 相似文献
87.
88.
Qiang Zhang Yu-hang Miao Teng Liu Yin-ling Yun Xiao-ya Sun Tao Yang Jie Sun 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):1023
3-arylcoumarins with different pharmacological properties widely exist in a variety of natural plants. The extensive research on 3-arylcoumarins was attributed to its therapeutic and relatively easy isolation. Therefore, 3-arylcoumarins can be recognised as useful structures for the design of novel compounds with potential pharmacological interest, particularly in the fields of anti-inflammatory, anti-cancer, antioxidant, Monoamine oxidase (MAO) enzyme inhibition, etc. The current review highlights the biological activities, design, and chemical synthetic methods of 3-arylcoumarins derivatives as well as their important natural product sources. 相似文献
89.
Hongchen Yan Junjie Xu Ilyas Ali Wei Zhang Ming Jiang Guiping Li Yong Teng Guangxun Zhu Yafei Cai 《Cell proliferation》2022,55(5)
Purpose and MaterialsCDK5RAP3 (CDK5 regulatory subunit associated protein 3) was originally identified as a binding protein of CDK5. It is a crucial gene controlling biological functions, such as cell proliferation, apoptosis, invasion, and metastasis. Although previous studies have also shown that CDK5RAP3 is involved in a variety of signalling pathways, however, the mechanism of CDK5RAP3 remains largely undefined. This study utilized MEFs from conditional knockout mice to inhibit CDK5RAP3 and knockdown CDK5RAP3 in MCF7 to explore the role of CDK5RAP3 in cell growth, mitosis, and cell death.ResultsCDK5RAP3 was found to be widely distributed throughout the centrosome, spindle, and endoplasmic reticulum, indicating that it is involved in regulating a variety of cellular activities. CDK5RAP3 deficiency resulted in instability of cell growth. CDK5RAP3 deficiency partly blocks the cell cycle in G2/M by downregulating CDK1 (Cyclin‐dependent kinase 1) and CCNB1 (Cyclin B1) expression levels. The cell proliferation rate was decreased, thereby slowing down the cell growth rate. Furthermore, the results showed that CDK5RAP3 interacts with RPL26 (ribosome protein L26) to regulate the mTOR pathway. CDK5RAP3 and RPL26 deficiency inhibited mTOR/p‐mTOR protein and induce autophagy, resulting in an upregulation of the percentage of apoptosis, and the upregulated percentage of apoptosis also slowed cell growth.ConclusionsOur experiments show that CDK5RAP3 interacts with RPL26 and maintains the stability of cell growth. It shows that CDK5RAP3 plays an important role in cell growth and can be used as the target of gene medicine.In normal, CDK5RAP3 is distributed in the centrosome, spindle and endoplasmic reticulum, the cells undergoes the growth and proliferation. However, when CDK5RAP3 is deficient, the cell cycle is blocked in G2/M and cell proliferation slows down, and the partial cycle block does not cause apoptosis. Additionally, CDK5RAP3 distributed in the endoplasmic reticulum combined with the deficiency of RPL26 will inhibit the mTOR pathway, aggravate autophagy and trigger apoptosis. 相似文献
90.
Mingshan Xue Teng Zhang Zhangkai J. Cheng Baojun Guo Yifeng Zeng Runpei Lin Peiyan Zheng Mingtao Liu Fengyu Hu Feng Li Wensheng Zhang Lu Li Qi Zhao Baoqing Sun Xiaoping Tang 《International journal of biological sciences》2022,18(12):4618
This study aimed to explore the clinical practice of phospholipid metabolic pathways in COVID-19. In this study, 48 COVID-19 patients and 17 healthy controls were included. Patients were divided into mild (n=40) and severe (n=8) according to their severity. Phospholipid metabolites, TCA circulating metabolites, eicosanoid metabolites, and closely associated enzymes and transfer proteins were detected in the plasma of all individuals using metabolomics and proteomics assays, respectively. 30 of the 33 metabolites found differed significantly (P<0.05) between patients and healthy controls (P<0.05), with D-dimmer significantly correlated with all of the lysophospholipid metabolites (LysoPE, LysoPC, LysoPI and LPA). In particular, we found that phosphatidylinositol (PI) and phosphatidylcholine (PC) could identify patients from healthy controls (AUC 0.771 and 0.745, respectively) and that the severity of the patients could be determined (AUC 0.663 and 0.809, respectively). The last measurement before discharge also revealed significant changes in both PI and PC. For the first time, our study explores the significance of the phospholipid metabolic system in COVID-19 patients. Based on molecular pathway mechanisms, three important phospholipid pathways related to Ceramide-Malate acid (Cer-SM), Lysophospholipid (LPs), and membrane function were established. Clinical values discovered included the role of Cer in maintaining the inflammatory internal environment, the modulation of procoagulant LPA by upstream fibrinolytic metabolites, and the role of PI and PC in predicting disease aggravation. 相似文献