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241.
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
242.
243.
Ning Xie Yunfan Bai Lu Qiao Yuru Bai Jian Wu Yan Li Mingzuo Jiang Bing Xu Zhen Ni Ting Yuan Yongquan Shi Kaichun Wu Feng Xu Jinhai Wang Lei Dong Na Liu 《Journal of cellular and molecular medicine》2021,25(8):4014-4027
The ADP-ribosylation factor-like proteins (ARLs) have been proved to regulate the malignant phenotypes of several cancers. However, the exact role of ARLs in gastric cancer (GC) remains elusive. In this study, we systematically investigate the expression status, interactive relations, potential pathways, genetic variations and clinical values of ARLs in GC. We find that ARLs are significantly dysregulated in GC and involved in various cancer-related pathways. Subsequently, machine learning models identify ARL4C as one of the two most significant clinical indicators among ARLs for GC. Furthermore, ARL4C silencing remarkably inhibits the growth and metastasis of GC cells both in vitro and in vivo. Moreover, enrichment analysis indicates that ARL4C is highly correlated with TGF-β1 signalling. Correspondingly, TGF-β1 treatment dramatically increases ARL4C expression and ARL4C knockdown inhibits the phosphorylation level of Smads, downstream factors of TGF-β1. Meanwhile, the coexpression of ARL4C and TGF-β1 worsens the prognosis of GC patients. Our work comprehensively demonstrates the crucial role of ARLs in the carcinogenesis of GC and the specific mechanisms underlying the GC-promoting effects of TGF-β1. More importantly, we uncover the great promise of ARL4C-targeted therapy in improving the efficacy of TGF-β1 inhibitors for GC patients. 相似文献
244.
Zhentao Yang Liang Zhang Hai Zhu Ke Zhou Hangxiang Wang Yuchen Wang Rong Su Danjing Guo Lin Zhou Xiao Xu Penghong Song Shusen Zheng Haiyang Xie 《Journal of cellular and molecular medicine》2021,25(7):3511-3523
Hepatocellular carcinoma (HCC) is one of the most aggressive tumours with marked fibrosis. Mycophenolate mofetil (MMF) was well-established to have antitumour and anti-fibrotic properties. To overcome the poor bioavailability of MMF, this study constructed two MMF nanosystems, MMF-LA@DSPE-PEG and MMF-LA@PEG-PLA, by covalently conjugating linoleic acid (LA) to MMF and then loading the conjugate into polymer materials, PEG5k-PLA8k and DSPE- PEG2k, respectively. Hepatocellular carcinoma cell lines and C57BL/6 xenograft model were used to examine the anti-HCC efficacy of nanoparticles (NPs), whereas NIH-3T3 fibroblasts and highly-fibrotic HCC models were used to explore the anti-fibrotic efficacy. Administration of NPs dramatically inhibited the proliferation of HCC cells and fibroblasts in vitro. Animal experiments revealed that MMF-LA@DSPE-PEG achieved significantly higher anti-HCC efficacy than free MMF and MMF-LA@PEG-PLA both in C57BL/6 HCC model and highly-fibrotic HCC models. Immunohistochemistry further confirmed that MMF-LA@DSPE-PEG dramatically reduced cancer-associated fibroblast (CAF) density in tumours, as the expression levels of alpha-smooth muscle actin (α-SMA), fibroblast activation protein (FAP) and collagen IV were significantly downregulated. In addition, we found the presence of CAF strongly correlated with increased HCC recurrence risk after liver transplantation. MMF-LA@DSPE-PEG might act as a rational therapeutic strategy in treating HCC and preventing post-transplant HCC recurrence. 相似文献
245.
Lisa R. Goldberg Emily J. Yao Julia C. Kelliher Eric R. Reed Jiayi Wu Cox Cory Parks Stacey L. Kirkpatrick Jacob A. Beierle Melanie M. Chen William E. Johnson Gregg E. Homanics Robert W. Williams Camron D. Bryant Megan K. Mulligan 《Genes, Brain & Behavior》2021,20(8):e12774
Psychostimulant (methamphetamine, cocaine) use disorders have a genetic component that remains mostly unknown. We conducted genome-wide quantitative trait locus (QTL) analysis of methamphetamine stimulant sensitivity. To facilitate gene identification, we employed a Reduced Complexity Cross between closely related C57BL/6 mouse substrains and examined maximum speed and distance traveled over 30 min following methamphetamine (2 mg/kg, i.p.). For maximum methamphetamine-induced speed following the second and third administration, we identified a single genome-wide significant QTL on chromosome 11 that peaked near the Cyfip2 locus (LOD = 3.5, 4.2; peak = 21 cM [36 Mb]). For methamphetamine-induced distance traveled following the first and second administration, we identified a genome-wide significant QTL on chromosome 5 that peaked near a functional intronic indel in Gabra2 coding for the alpha-2 subunit of the GABA-A receptor (LOD = 3.6–5.2; peak = 34–35 cM [66–67 Mb]). Striatal cis-expression QTL mapping corroborated Gabra2 as a functional candidate gene underlying methamphetamine-induced distance traveled. CRISPR/Cas9-mediated correction of the mutant intronic deletion on the C57BL/6J background to the wild-type C57BL/6NJ allele was sufficient to reduce methamphetamine-induced locomotor activity toward the wild-type C57BL/6NJ-like level, thus validating the quantitative trait variant (QTV). These studies show the power and efficiency of Reduced Complexity Crosses in identifying causal variants underlying complex traits. Functionally restoring Gabra2 expression decreased methamphetamine stimulant sensitivity and supports preclinical and human genetic studies implicating the GABA-A receptor in psychostimulant addiction-relevant traits. Importantly, our findings have major implications for studying psychostimulants in the C57BL/6J strain—the gold standard strain in biomedical research. 相似文献
246.
Mao Ting Zhu Mingdong Ahmad Shakeel Ye Guoyou Sheng Zhonghua Hu Shikai Jiao Guiai Xie Lihong Tang Shaoqing Wei Xiangjin Hu Peisong Shao Gaoneng 《Molecular breeding : new strategies in plant improvement》2021,41(10):1-14
Molecular Breeding - The stem color of young mung bean is a very useful tool in germplasm identification. Flowering time and plant height (PH) are known to be strongly correlated with crop adaption... 相似文献
247.
Emily B. Cohen Kyle G. Horton Peter P. Marra Hannah L. Clipp Andrew Farnsworth Jaclyn A. Smolinsky Daniel Sheldon Jeffrey J. Buler 《Ecology letters》2021,24(1):38-49
Migrating birds require en route habitats to rest and refuel. Yet, habitat use has never been integrated with passage to understand the factors that determine where and when birds stopover during spring and autumn migration. Here, we introduce the stopover‐to‐passage ratio (SPR), the percentage of passage migrants that stop in an area, and use 8 years of data from 12 weather surveillance radars to estimate over 50% SPR during spring and autumn through the Gulf of Mexico and Atlantic coasts of the south‐eastern US, the most prominent corridor for North America’s migratory birds. During stopovers, birds concentrated close to the coast during spring and inland in forested landscapes during autumn, suggesting seasonal differences in habitat function and highlighting the vital role of stopover habitats in sustaining migratory communities. Beyond advancing understanding of migration ecology, SPR will facilitate conservation through identification of sites that are disproportionally selected for stopover by migrating birds. 相似文献
248.
Gacek Elizabeth Bermel Emily A. Ellingson Arin M. Barocas Victor H. 《Biomechanics and modeling in mechanobiology》2021,20(4):1445-1457
Biomechanics and Modeling in Mechanobiology - The human lumbar facet capsule, with the facet capsular ligament (FCL) that forms its primary constituent, is a common source of lower back pain. Prior... 相似文献
249.
林窗环境异质性导致群落物种多样性与系统发育多样性(phylogenetic diversity, PD)存在差异, 研究不同大小的林窗中群落的物种多样性与系统发育多样性有助于揭示林下生物多样性的形成及维持机制。本文以格氏栲(Castanopsis kawakamii)天然林为研究对象, 通过Pearson相关性分析与广义线性模型探讨了林窗内物种多样性与系统发育多样性间的相互关系及其环境影响因素。结果表明: (1)大林窗(面积 > 200 m2)植物种类及多度均高于中林窗(50 m2 ≤ 面积 < 100 m2)、小林窗(30 m2 ≤ 面积 < 50 m2)和非林窗(面积 = 100 m2)。大林窗群落系统发育结构趋于发散, 中、小林窗和非林窗群落系统发育结构受到生境过滤和竞争排斥综合作用。(2)群落系统发育多样性指数与物种丰富度(species richness, SR)、Margalef丰富度指数和Shannon-Wiener指数均呈显著正相关, 这与林窗内稀有种种类组成多于优势种有关。(3)林窗面积对物种多样性存在显著正效应; 土壤全氮含量对系统发育多样性和系统发育结构存在显著正效应。林窗形成提高了格氏栲天然林群落物种多样性和系统发育多样性, 林窗面积与土壤全氮共同驱动了格氏栲天然林林窗物种多样性和系统发育多样性的变化。 相似文献
250.
全球传粉昆虫多样性正在下降, 如何保障农林生态系统传粉功能是当前研究的热点。理论上说, 传粉功能不仅与生态系统的传粉昆虫多样性相关, 还与生态系统的调节能力有关。近年来, 学者们逐渐认识到授粉生态弹性对传粉功能的影响。本文在回顾已有研究的基础之上, 总结传粉昆虫授粉生态弹性的内涵, 厘清授粉生态弹性与工程弹性、稳定性和抗性的异同。目前, 学者对授粉生态弹性形成机制开展广泛探讨, 提出功能冗余假说、密度补偿假说、响应多样性假说、连接周转假说和跨尺度弹性假说, 但这5个假说间的关系仍不清楚, 存在一词多义、词意混淆等现象。我们依次阐述功能冗余假说、密度补偿假说、响应多样性假说、连接周转假说和跨尺度弹性假说, 介绍不同假说中授粉生态弹性形成过程、研究热点和发展动态。通过解析授粉生态弹性的形成机制可知, 5个假说在内涵上存在紧密联系, 它们从不同空间尺度和研究对象下解释传粉昆虫授粉生态弹性的形成机制。未来授粉生态弹性研究将整合传粉昆虫群落动态和传粉功能动态的量化方法, 通过实验验证5个假说的合理性, 并揭示不同假说间的联系, 由此阐明授粉生态弹性的发生条件、形成阈值和动态规律。随着研究的深入, 授粉生态弹性理论有望用于指导农林生态系统传粉功能的经营管理。 相似文献