全文获取类型
收费全文 | 108107篇 |
免费 | 8387篇 |
国内免费 | 9040篇 |
专业分类
125534篇 |
出版年
2024年 | 241篇 |
2023年 | 1419篇 |
2022年 | 3270篇 |
2021年 | 5519篇 |
2020年 | 3786篇 |
2019年 | 4686篇 |
2018年 | 4439篇 |
2017年 | 3240篇 |
2016年 | 4600篇 |
2015年 | 6679篇 |
2014年 | 7849篇 |
2013年 | 8306篇 |
2012年 | 9982篇 |
2011年 | 8984篇 |
2010年 | 5550篇 |
2009年 | 4971篇 |
2008年 | 5713篇 |
2007年 | 5138篇 |
2006年 | 4456篇 |
2005年 | 3493篇 |
2004年 | 2970篇 |
2003年 | 2720篇 |
2002年 | 2273篇 |
2001年 | 1866篇 |
2000年 | 1696篇 |
1999年 | 1671篇 |
1998年 | 1037篇 |
1997年 | 1002篇 |
1996年 | 941篇 |
1995年 | 821篇 |
1994年 | 787篇 |
1993年 | 617篇 |
1992年 | 818篇 |
1991年 | 618篇 |
1990年 | 466篇 |
1989年 | 443篇 |
1988年 | 354篇 |
1987年 | 344篇 |
1986年 | 266篇 |
1985年 | 286篇 |
1984年 | 156篇 |
1983年 | 161篇 |
1982年 | 99篇 |
1981年 | 85篇 |
1980年 | 60篇 |
1979年 | 77篇 |
1977年 | 59篇 |
1975年 | 56篇 |
1974年 | 52篇 |
1973年 | 56篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
991.
Yuyu Li Yuxin Zhang Jianrong Lu Yong Yin Jun Xie Biao Xu 《Journal of cellular and molecular medicine》2021,25(17):8087-8094
Inflammatory responses play a vital role in the onset and development of atherosclerosis, and throughout the entire process of the chronic disease. The inflammatory responses in atherosclerosis are mainly mediated by the NLRP3 inflammasome and its downstream inflammatory factors. As a powerful anti-inflammatory medicine, colchicine has a history of more than 200 years in clinical application and is the first-choice treatment for immune diseases such as gout and familial Mediterranean fever. In atherosclerosis, colchicine can inhibit the assembly and activation of NLRP3 inflammasome via various mechanisms to effectively reduce the expression of inflammatory factors, thereby reducing the inflammation. Recent clinical trials show that a low dose of colchicine (0.5 mg per day) has a certain protective effect in stable angina patients or those with acute myocardial infarction after PCI. This article summarizes and discusses the mechanisms of colchicine in the treatment of atherosclerosis and the latest research progress. 相似文献
992.
993.
994.
Hongtao Cheng Mengyu Hao Bingli Ding Desheng Mei Wenxiang Wang Hui Wang Rijin Zhou Jia Liu Chao Li Qiong Hu 《Plant biotechnology journal》2021,19(1):87-97
CRISPR/Cas‐base editing is an emerging technology that could convert a nucleotide to another type at the target site. In this study, A3A‐PBE system consisting of human A3A cytidine deaminase fused with a Cas9 nickase and uracil glycosylase inhibitor was established and developed in allotetraploid Brassica napus. We designed three sgRNAs to target ALS, RGA and IAA7 genes, respectively. Base‐editing efficiency was demonstrated to be more than 20% for all the three target genes. Target sequencing results revealed that the editing window ranged from C1 to C10 of the PAM sequence. Base‐edited plants of ALS conferred high herbicide resistance, while base‐edited plants of RGA or IAA7 exhibited decreased plant height. All the base editing could be genetically inherited from T0 to T1 generation. Several Indel mutations were confirmed at the target sites for all the three sgRNAs. Furthermore, though no C to T substitution was detected at the most potential off‐target sites, large‐scale SNP variations were determined through whole‐genome sequencing between some base‐edited and wild‐type plants. These results revealed that A3A‐PBE base‐editing system could effectively convert C to T substitution with high‐editing efficiency and broadened editing window in oilseed rape. Mutants for ALS, IAA7 and RGA genes could be potentially applied to confer herbicide resistance for weed control or with better plant architecture suitable for mechanic harvesting. 相似文献
995.
In this article, a simple, effective chemiluminescence (CL) method for the detection of methylparaben (MP) in cosmetic samples was developed based on an IO4?–H2O2–carbon nitrogen quantum dots (CNQDs) system without a separation process. The results indicated that the redox reaction between periodate and hydrogen peroxide released hydroxide radicals and superoxide radical anions in the presence of bicarbonate. These two radicals were responsible for the formation of excited luminophor CNQD* with a maximum wavelength at 480 nm. Due to the competitive reaction with hydroxide radicals, CL intensity was markedly diminished in the presence of MP. The relative standard deviation in the intraday assay was below 5.5% (n = 9), and the detection limit was as low as 0.50 μmol/L. The proposed method allowed for the successful, selective determination of MP in cosmetics. 相似文献
996.
Ma Jiachi Liang Wanqing Qiang Yaosheng Li Lei Du Jun Pan Chengwu Chen Bangling Zhang Chensong Chen Yuzhong Wang Qingkang 《Cell communication and signaling : CCS》2021,19(1):1-12
Wnt signaling plays key roles in cellular and physiological processes, including cell proliferation, differentiation and migration during development and tissue homeostasis in adults. This pathway can be defined as Wnt/β-catenin-dependent or β-catenin-independent or “non-canonical”, both signaling are involved in neurite and synapse development/maintenance. Porcupine (PORCN), an acylase that o-acylates Wnt ligands, a major modification in secretion and interaction with its receptors. We use Wnt-C59, a specific PORCN inhibitor, to block the secretion of endogenous Wnts in embryonic hippocampal neurons (DIV 4). Under these conditions, the activity of exogenous Wnt ligands on the complexity of the dendritic tree and axonal polarity were evaluated Cultured primary embryonic hippocampal neurons obtained from Sprague–Dawley rat fetuses (E18), were cultured until day in vitro (DIV) 4 (according to Banker´s protocol) and treated with Wnt-C59 for 24 h, Wnt ligands were added to the cultures on DIV 3 for 24 h. Dendritic arbors and neurites were analysis by fluorescence microscopy. Transfection with Lipofectamine 2000 on DIV 2 of plasmid expressing eGFP and KIF5-Cherry was carried out to evaluate neuronal polarity. Immunostaining was performed with MAP1B and Tau protein. Immunoblot analysis was carried out with Wnt3a, β-catenin and GSK-3β (p-Ser9). Quantitative analysis of dendrite morphology was carried out with ImageJ (NIH) software with Neuron J Plugin. We report, here, that Wnt-C59 treatment changed the morphology of the dendritic arbors and neurites of embryonic hippocampal neurons, with decreases β-catenin and Wnt3a and an apparent increase in GSK-3β (p-Ser9) levels. No effect was observed on axonal polarity. In sister cultures, addition of exogenous Wnt3a, 5a and 7a ligands rescued the changes in neuronal morphology. Wnt3a restored the length of neurites to near that of the control, but Wnt7a increased the neurite length beyond that of the control. Wnt5a also restored the length of neurites relative to Wnt concentrations. Results indicated that Wnt ligands, added exogenously, restored dendritic arbor complexity in embryonic hippocampal neurons, previously treated with a high affinity specific Porcupine inhibitor. We proposed that PORCN is an emerging molecular target of interest in the search for preclinical options to study and treat Wnt-related diseases. 相似文献
997.
Phytohormones mediate plant development and responses to stresses caused by biotic agents or abiotic factors. The functions of phytohormones in responses to viral infection have been intensively studied, and the emerging picture of complex mechanisms provides insights into the roles that phytohormones play in defense regulation as a whole. These hormone signaling pathways are not simple linear or isolated cascades, but exhibit crosstalk with each other. Here, we summarized the current understanding of recent advances for the classical defense hormones salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) and also the roles of abscisic acid (ABA), auxin, gibberellic acid (GA), cytokinins (CKs), and brassinosteroids (BRs) in modulating plant–virus interactions. 相似文献
998.
Wang Che Huang Lili Li Ruojin Wang Ying Wu Xiaoxue Shang Dejing 《International journal of peptide research and therapeutics》2021,27(4):2291-2301
International Journal of Peptide Research and Therapeutics - Multidrug resistance (MDR) is one of the major obstacles to efficient chemotherapy against cancers, resulting from the overexpression of... 相似文献
999.
Lv Yufeng Li Feng Zhi Dexian 《International journal of peptide research and therapeutics》2021,27(3):1763-1768
International Journal of Peptide Research and Therapeutics - Diabetes is a metabolic disorder caused by defects in insulin production and insulin activity. l-Carnosine is a dipeptide containing... 相似文献
1000.
Hong-Wei Zhang Yi Shi Ji-Bin Liu Hui-Min Wang Pei-Yao Wang Zhi-Jun Wu Liu Li Li-Peng Gu Ping-Sheng Cao Gao-Ren Wang Yu-Shui Ma Da Fu 《Journal of cellular and molecular medicine》2021,25(8):3699-3713
MicroRNA-24-3p (miR-24-3p) has been implicated as a key promoter of chemotherapy resistance in numerous cancers. Meanwhile, cancer-associated fibroblasts (CAFs) can secret exosomes to transfer miRNAs, which mediate tumour development. However, little is known regarding the molecular mechanism of CAF-derived exosomal miR-24-3p in colon cancer (CC). Hence, this study intended to characterize the functional relevance of CAF-derived exosomal miR-24-3p in CC cell resistance to methotrexate (MTX). We identified differentially expressed HEPH, CDX2 and miR-24-3p in CC through bioinformatics analyses, and validated their expression in CC tissues and cells. The relationship among HEPH, CDX2 and miR-24-3p was verified using ChIP and dual-luciferase reporter gene assays. Exosomes were isolated from miR-24-3p inhibitor–treated CAFs (CAFs-exo/miR-24-3p inhibitor), which were used in combination with gain-of-function and loss-of-function experiments and MTX treatment. CCK-8, flow cytometry and colony formation assays were conducted to determine cell viability, apoptosis and colony formation, respectively. Based on the findings, CC tissues and cells presented with high expression of miR-24-3p and low expression of HEPH and CDX2. CDX2 was a target gene of miR-24-3p and could up-regulate HEPH. Under MTX treatment, overexpressed CDX2 or HEPH and down-regulated miR-24-3p reduced cell viability and colony formation and elevated cell apoptosis. Furthermore, miR-24-3p was transferred into CC cells via CAF-derived exosomes. CAF-derived exosomal miR-24-3p inhibitor diminished cell viability and colony formation and increased cell apoptosis in vitro and inhibited tumour growth in vivo under MTX treatment. Altogether, CAF-derived exosomal miR-24-3p accelerated resistance of CC cells to MTX by down-regulating CDX2/HEPH axis. 相似文献