全文获取类型
收费全文 | 36058篇 |
免费 | 4675篇 |
国内免费 | 16787篇 |
专业分类
57520篇 |
出版年
2024年 | 386篇 |
2023年 | 1183篇 |
2022年 | 2021篇 |
2021年 | 2314篇 |
2020年 | 2177篇 |
2019年 | 2421篇 |
2018年 | 1761篇 |
2017年 | 1655篇 |
2016年 | 1757篇 |
2015年 | 2459篇 |
2014年 | 3291篇 |
2013年 | 2971篇 |
2012年 | 4006篇 |
2011年 | 3951篇 |
2010年 | 2934篇 |
2009年 | 2916篇 |
2008年 | 3200篇 |
2007年 | 2878篇 |
2006年 | 2577篇 |
2005年 | 2080篇 |
2004年 | 1637篇 |
2003年 | 1339篇 |
2002年 | 1144篇 |
2001年 | 949篇 |
2000年 | 918篇 |
1999年 | 624篇 |
1998年 | 346篇 |
1997年 | 207篇 |
1996年 | 202篇 |
1995年 | 142篇 |
1994年 | 135篇 |
1993年 | 115篇 |
1992年 | 90篇 |
1991年 | 69篇 |
1990年 | 73篇 |
1989年 | 50篇 |
1988年 | 63篇 |
1987年 | 37篇 |
1986年 | 42篇 |
1985年 | 58篇 |
1984年 | 36篇 |
1983年 | 26篇 |
1982年 | 55篇 |
1981年 | 26篇 |
1980年 | 15篇 |
1964年 | 13篇 |
1963年 | 12篇 |
1957年 | 14篇 |
1953年 | 13篇 |
1950年 | 19篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Shuyu Liu Lei Zhang Yupeng Sang Qiang Lai Xinxin Zhang Changfu Jia Zhiqin Long Jiali Wu Tao Ma Kangshan Mao Nathaniel R Street Pr K Ingvarsson Jianquan Liu Jing Wang 《Molecular biology and evolution》2022,39(2)
Hybridization and resulting introgression are important processes shaping the tree of life and appear to be far more common than previously thought. However, how the genome evolution was shaped by various genetic and evolutionary forces after hybridization remains unresolved. Here we used whole-genome resequencing data of 227 individuals from multiple widespread Populus species to characterize their contemporary patterns of hybridization and to quantify genomic signatures of past introgression. We observe a high frequency of contemporary hybridization and confirm that multiple previously ambiguous species are in fact F1 hybrids. Seven species were identified, which experienced different demographic histories that resulted in strikingly varied efficacy of selection and burdens of deleterious mutations. Frequent past introgression has been found to be a pervasive feature throughout the speciation of these Populus species. The retained introgressed regions, more generally, tend to contain reduced genetic load and to be located in regions of high recombination. We also find that in pairs of species with substantial differences in effective population size, introgressed regions are inferred to have undergone selective sweeps at greater than expected frequencies in the species with lower effective population size, suggesting that introgression likely have higher potential to provide beneficial variation for species with small populations. Our results, therefore, illustrate that demography and recombination have interplayed with both positive and negative selection in determining the genomic evolution after hybridization. 相似文献
992.
60Coγ射线辐照处理对枇杷次生枝果实品质性状的影响 总被引:5,自引:1,他引:4
探讨了60Coγ射线照射解放钟枇杷枝条,对次生枝果实外观品质和口感品质性状的诱变规律。结果表明:在14.4 Gy~28.8 Gy辐照剂量范围内,对风味品质、果肉颜色、果皮颜色、锈斑、肉质、汁液等有较强的诱变效应(诱变频率0.48%~44.06%);诱变效应为风味>果肉颜色>果皮颜色>肉质>锈斑>汁液,有益诱变效应为:风味>果皮颜色>汁液>肉质;综合比较认为,要改善解放钟枇杷果实外观品质和口感品质,宜选用24.0 Gy左右的辐照剂量。 相似文献
993.
Shigang Qiao Lei Hong Yongming Zhu Jun Zha An Wang Jia Qiu Wei Li Chen Wang Jianzhong An Huiling Zhang 《Cell death & disease》2022,13(2)
Receptor-interacting protein kinase 1 (RIPK1) and 3 (RIPK3) are critical regulators of programmed necrosis or necroptosis. However, the role of the RIPK1/RIPK3 signaling pathway in myocardial fibrosis and related diabetic cardiomyopathy is still unclear. We hypothesized that RIPK1/RIPK3 activation mediated myocardial fibrosis by impairing the autophagic flux. To this end, we established in vitro and in vivo models of type 2 diabetes mellitus with high glucose fat (HGF) medium and diet respectively. HGF induced myocardial fibrosis, and impaired cardiac diastolic and systolic function by activating the RIPK1/RIPK3 pathway, which increased the expression of autophagic related proteins such as LC3-II, P62 and active-cathepsin D. Inhibition of RIPK1 or RIPK3 alleviated HGF-induced death and fibrosis of cardiac fibroblasts by restoring the impaired autophagic flux. The autophagy blocker neutralized the effects of the RIPK1 inhibitor necrostatin-1 (Nec-1) and RIPK3 inhibitor GSK872 (GSK). RIPK1/RIPK3 inhibition respectively decreased the levels of RIPK3/p-RIPK3 and RIPK1/p-RIPK1. P62 forms a complex with RIPK1-RIPK3 and promotes the binding of RIPK1 and RIPK3, silencing of RIPK1 decreased the association of RIPK1 with P62 and the binding of P62 to LC3. Furthermore, inhibition of both kinases in combination with a low dose of Nec-1 and GSK in the HGF-treated fibroblasts significantly decreased cell death and fibrosis, and restored the autophagic flux. In the diabetic rat model, Nec-1 (1.65 mg/kg) treatment for 4 months markedly alleviated myocardial fibrosis, downregulated autophagic related proteins, and improved cardiac systolic and diastolic function. In conclusion, HGF induces myocardial fibrosis and cardiac dysfunction by activating the RIPK1-RIPK3 pathway and by impairing the autophagic flux, which is obviated by the pharmacological and genetic inhibition of RIPK1/RIPK3.Subject terms: Necroptosis, Diabetes complications 相似文献
994.
995.
Wuping Yang Jingcheng Zhou Zedan Zhang Kenan Zhang Yawei Xu Lei Li Lin Cai Yanqing Gong Kan Gong 《International journal of biological sciences》2022,18(6):2583
Background: The current studies only indicated that long non-coding RNA (lncRNA) APCDD1L-AS1, as a novel lncRNA, may play a role in oral squamous cell carcinoma and lung cancer. However, its potential role in clear cell renal cell carcinoma (ccRCC) and its possible mechanism of action remain vague.Methods: TCGA-KIRC and GEO data and qRT-PCR and pyrosequencing results of clinical specimens were used to identify the expression level and DNA methylation status of APCDD1L-AS1. The effects of APCDD1L-AS1 overexpression on ccRCC growth and metastasis were determined by function experiments. Western blot and Tandem mass tags (TMT) were utilized to explore the relationship between APCDD1L-AS1 and VHL expression and its downstream underlying mechanisms.Results: The expression of APCDD1L-AS1 was downregulated in ccRCC. Decreased APCDD1L-AS1 expression was related to higher tumor stage and histological grade and shorter RFS (Relapse-free survival). Besides, APCDD1L-AS1 overexpression restrained the growth and metastasis of ccRCC cells in vitro and in vivo. Moreover, reduced APCDD1L-AS1 expression could be caused by DNA hypermethylation and loss of von Hippel Lindau (VHL) protein expression. Furthermore, the dysregulation of histones expression caused by APCDD1L-AS1 overexpression may be one of the important mechanisms to suppress the progression of ccRCC.Conclusion: APCDD1L-AS1 was able to inhibit the progression of ccRCC, and its decreased expression could be caused by DNA hypermethylation and loss of VHL protein expression. Therefore, APCDD1L-AS1 may serve as a new therapeutic target in the treatment of ccRCC. 相似文献
996.
Zhongyi Fan Jingjing Duan Pu Luo Ling Shao Qiong Chen Xiaohua Tan Lei Zhang Xiaojie Xu 《Cell death & disease》2022,13(4)
Risk of metastasis is increased by the presence of chromosome 3 monosomy in uveal melanoma (UM). This study aimed to identify more accurate biomarker for risk of metastasis in UM. A total of 80 patients with UM from TCGA were assigned to two groups based on the metastatic status, and bioinformatic analyses were performed to search for critical genes for risk of metastasis. SLC25A38, located on chromosome 3, was the dominant downregulated gene in metastatic UM patients. Low expression of SLC25A38 was an independent predictive and prognostic factor in UM. The predictive potential of SLC25A38 expression was superior to that of pervious reported biomarkers in both TCGA cohort and cohort. Subsequently, its role in promoting metastasis was explored in vitro and in vivo. Knock-out of SLC25A38 could enhance the migration ability of UM cells, and promote distant metastasis in mice models. Through the inhibition of CBP/HIF-mediated pathway followed by the suppression of pro-angiogenic factors, SLC25A38 was situated upstream of metastasis-related pathways, especially angiogenesis. Low expression of SLC25A38 promotes angiogenesis and metastasis, and identifies increased metastatic risk and worse survival in UM patients. This finding may further improve the accuracy of prognostic prediction for UM.Subject terms: GSE22138Eye cancer, Prognostic markers 相似文献
997.
Lei Chen Ghassan K. Abou-Alfa Bo Zheng Jing-Feng Liu Jian Bai Lu-Tao Du Yun-Song Qian Rong Fan Xiao-Long Liu Lin Wu Jin-Lin Hou Hong-Yang Wang The PreCar Team 《Cell research》2021,31(5):589-592
Dear Editor,
Hepatocellular carcinoma (HCC) is the second most deadly cancer worldwide.1 Cirrhosis of different causes predisposes patients to HCC,increasing th... 相似文献
998.
Lin Peng Min Zhao Tianqi Liu Jiangbo Chen Pin Gao Lei Chen Pu Xing Zaozao Wang Jiabo Di Qiang Xu Hong Qu Beihai Jiang Xiangqian Su 《Cell death & disease》2022,13(4)
Genomic instability plays a key role in the initiation and progression of colorectal cancer (CRC). Although cancer driver genes in CRC have been well characterized, identifying novel genes associated with carcinogenesis and treatment remains challenging because of tumor heterogeneity. Here, we analyzed the genomic alterations of 45 samples from CRC patients in northern China by whole-exome sequencing. In addition to the identification of six well-known CRC driver genes (APC, TP53, KRAS, FBXW7, PIK3CA, and PABPC), two tumor-related genes (MTCH2 and HSPA6) were detected, along with RRP7A and GXYLT1, which have not been previously linked to cancer. GXYLT1 was mutated in 40% (18/45) of the samples in our cohort. Functionally, GXYLT1 promoted migration and invasion in vitro and metastasis in vivo, while the GXYLT1S212* mutant induced significantly greater effect. Furthermore, both GXYLT1 and GXYLT1S212* interacted with ERK2. GXYLT1 induced metastasis via a mechanism involving the Notch and MAPK pathways, whereas the GXYLT1S212* mutant mainly promoted metastasis by activating the MAPK pathway. We propose that GXYLT1 acts as a novel metastasis-associated driver gene and GXYLT1S212* might serve as a potential indicator for therapies targeting the MAPK pathway in CRC.Subject terms: Cancer genomics, Colorectal cancer, Metastasis, Oncogenes, Cell signalling 相似文献
999.
Siwen Dong Yujin Shi Xiaojing Dong Xia Xiao Jianli Qi Lili Ren Zichun Xiang Zhuo Zhou Jianwei Wang Xiaobo Lei 《The Journal of biological chemistry》2022,298(5)
Pyroptosis is an inflammatory form of programmed cell death that is executed by the gasdermin (GSDM)-N domain of GSDM family proteins, which form pores in the plasma membrane. Although pyroptosis acts as a host defense against invasive pathogen infection, its role in the pathogenesis of enterovirus 71 (EV71) infection is unclear. In the current study, we found that EV71 infection induces cleavage of GSDM E (GSDME) by using western blotting analysis, an essential step in the switch from caspase-3-mediated apoptosis to pyroptosis. We show that this cleavage is independent of the 3C and 2A proteases of EV71. However, caspase-3 activation is essential for this cleavage, as GSDME could not be cleaved in caspase-3-KO cells upon EV71 infection. Further analyses showed that EV71 infection induced pyroptosis in WT cells but not in caspase-3/GSDME double-KO cells. Importantly, GSDME is required to induce severe disease during EV71 infection, as GSDME deficiency in mice was shown to alleviate pathological symptoms. In conclusion, our results reveal that GSDME is important for the pathogenesis of EV71 via mediating initiation of pyroptosis. 相似文献
1000.
丛枝菌根真菌的三个我国新记录种 总被引:4,自引:1,他引:3
象牙白球囊霉(图1~3)Glomus eburneum Kennedy,Stutz&Morton,Mycologia,91(6):1083~1093,1999.孢子透明-象牙白色,圆形,近圆形,直径35~120μm,或不规则形,35~60×100~120μm。孢壁2层,第一层无色透明,厚1~2μm,老孢子中该层壁易缺失。第二层壁,层状透明,厚1.0~2.5μm,压碎孢子该层壁易皱缩而与第一层壁分开。连孢菌丝无色透明,宽2~5μm,内含物油状。连孢菌丝有隔包住内含物,Melzer’s试剂中孢子无染色反应。标本号:B1,B4,B7,B10,Z2,Z3,Z6,Z9,Z10,Z12,N3,N6,N9,N11。从莱阳农学院长期定位试验田玉米和小麦根际土壤中分离得到。海得拉… 相似文献