全文获取类型
收费全文 | 11656篇 |
免费 | 1036篇 |
国内免费 | 1911篇 |
专业分类
14603篇 |
出版年
2024年 | 56篇 |
2023年 | 216篇 |
2022年 | 432篇 |
2021年 | 729篇 |
2020年 | 541篇 |
2019年 | 646篇 |
2018年 | 632篇 |
2017年 | 454篇 |
2016年 | 551篇 |
2015年 | 902篇 |
2014年 | 968篇 |
2013年 | 956篇 |
2012年 | 1192篇 |
2011年 | 1050篇 |
2010年 | 658篇 |
2009年 | 607篇 |
2008年 | 680篇 |
2007年 | 577篇 |
2006年 | 484篇 |
2005年 | 430篇 |
2004年 | 359篇 |
2003年 | 309篇 |
2002年 | 244篇 |
2001年 | 120篇 |
2000年 | 132篇 |
1999年 | 117篇 |
1998年 | 87篇 |
1997年 | 104篇 |
1996年 | 83篇 |
1995年 | 54篇 |
1994年 | 48篇 |
1993年 | 23篇 |
1992年 | 24篇 |
1991年 | 21篇 |
1990年 | 23篇 |
1989年 | 12篇 |
1988年 | 15篇 |
1987年 | 11篇 |
1986年 | 8篇 |
1985年 | 10篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 13篇 |
1976年 | 2篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1965年 | 1篇 |
1950年 | 5篇 |
1911年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
91.
Jun Liu Junchen Chen Yadan Zhong Xiaoling Yu Ping Lu Jianqi Feng Xin Zhang Shufeng Ma Chao Yang Bin Yang Zhili Rong 《蛋白质与细胞》2021,12(8):653-660
Dear Editor,
Primary localized cutaneous amyloidosis (PLCA) is a skin-limited disorder characterized by deposition of amyloid material in the superficial dermis.According to clinical characteristics,PLCA is divided into lichen,macular,and nodular amyloidosis.PLCA is found worldwide but has a higher incidence in South America and Southeast Asia,such as in Brazil and China (Chang et al.,2014;Tey et al.,2016). 相似文献
92.
Yuxin Zhang Zhonglong Liu Kexin Wang Shenji Lu Shuai Fan Lili Xu Bin Cai 《International journal of biological sciences》2021,17(7):1837
Joint capsule fibrosis caused by excessive inflammation results in post-traumatic joint contracture (PTJC). Transforming growth factor (TGF)-β1 plays a key role in PTJC by regulating fibroblast functions, however, cytokine-induced TGF-β1 expression in specific cell types remains poorly characterized. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in inflammation- and fibrosis-associated pathophysiology. In this study, we investigated whether MIF can facilitate TGF-β1 production from fibroblasts and regulate joint capsule fibrosis following PTJC. Our data demonstrated that MIF and TGF-β1 significantly increased in fibroblasts of injured rat posterior joint capsules. Treatment the lesion sites with MIF inhibitor 4-Iodo-6-phenylpyrimidine (4-IPP) reduced TGF-β1 production and relieved joint capsule inflammation and fibrosis. In vitro, MIF facilitated TGF-β1 expression in primary joint capsule fibroblasts by activating mitogen-activated protein kinase (MAPK) (P38, ERK) signaling through coupling with membrane surface receptor CD74, which in turn affected fibroblast functions and promoted MIF production. Our results reveal a novel function of trauma-induced MIF in the occurrence and development of joint capsule fibrosis. Further investigation of the underlying mechanism may provide potential therapeutic targets for PTJC. 相似文献
93.
Xing Liu Yijie Ma Kathleen Voss Michiel van Gent Ying Kai Chan Michaela U. Gack Michael Gale Jr Bin He 《PLoS pathogens》2021,17(3)
RIG-I and MDA5 are cytoplasmic RNA sensors that mediate cell intrinsic immunity against viral pathogens. While it has been well-established that RIG-I and MDA5 recognize RNA viruses, their interactive network with DNA viruses, including herpes simplex virus 1 (HSV-1), remains less clear. Using a combination of RNA-deep sequencing and genetic studies, we show that the γ134.5 gene product, a virus-encoded virulence factor, enables HSV growth by neutralization of RIG-I dependent restriction. When expressed in mammalian cells, HSV-1 γ134.5 targets RIG-I, which cripples cytosolic RNA sensing and subsequently suppresses antiviral gene expression. Rather than inhibition of RIG-I K63-linked ubiquitination, the γ134.5 protein precludes the assembly of RIG-I and cellular chaperone 14-3-3ε into an active complex for mitochondrial translocation. The γ134.5-mediated inhibition of RIG-I-14-3-3ε binding abrogates the access of RIG-I to mitochondrial antiviral-signaling protein (MAVS) and activation of interferon regulatory factor 3. As such, unlike wild type virus HSV-1, a recombinant HSV-1 in which γ134.5 is deleted elicits efficient cytokine induction and replicates poorly, while genetic ablation of RIG-I expression, but not of MDA5 expression, rescues viral growth. Collectively, these findings suggest that viral suppression of cytosolic RNA sensing is a key determinant in the evolutionary arms race of a large DNA virus and its host. 相似文献
94.
Dechuang Jiao Jingyang Zhang Ping Chen Xuhui Guo Jianghua Qiao Jiujun Zhu Lina Wang Zhenduo Lu Zhenzhen Liu 《Journal of cellular and molecular medicine》2021,25(1):397-410
Recent reports showed that haematological and neurological expressed 1-like (HN1L) gene participated in tumorigenesis and tumour invasion. However, the expression and role of HN1L in breast cancer remain to be investigated. Here, bioinformatics, western blot and immunohistochemistry were used to detect the expression of HN1L in breast cancer. Wound healing, transwell assay, immunofluorescence assay and mass spectrum were used to explore the role and mechanism of HN1L on the migration and invasion of breast cancer, which was confirmed in vivo using a nude mice model. Results showed that HN1L was significantly over-expressed in breast cancer tissues, which was positively correlated with M metastasis of breast cancer patients. Silencing HN1L significantly inhibited the invasion and metastasis of breast cancer cells in vitro and lung metastasis in nude mice metastasis model of breast cancer. Mechanistically, HN1L interacted with HSPA9 and affected the expression of HMGB1, playing a key role in promoting the invasion and metastasis of breast cancer cell. These results suggested that HN1L was an appealing drug target for breast cancer. 相似文献
95.
Cheng Chu Gang Xu Xiaocong Li Zuowei Duan Lihong Tao Hongxia Cai Ming Yang Xinjiang Zhang Bin Chen Yanyu Zheng Hongcan Shi Xiaoyu Li 《Journal of cellular and molecular medicine》2021,25(1):110-119
Shear stress was reported to regulate the expression of AC007362, but its underlying mechanisms remain to be explored. In this study, to isolate endothelial cells of blood vessels, unruptured and ruptured intracranial aneurysm (IA) tissues were collected from IA patients. Subsequently, quantitative real-time PCR (qRT-PCR), Western blot and luciferase assay were performed to investigate the relationships between AC007362, miRNAs-493 and monocyte chemoattractant protein-1 (MCP-1) in human umbilical vein endothelial cells (HUVECs) exposed to shear stress. Reduced representation bisulphite sequencing (RRBS) was performed to assess the level of DNA methylation in AC007362 promoter. Accordingly, AC007362 and MCP-1 were significantly up-regulated while miR-493 was significantly down-regulated in HUVECs exposed to shear stress. AC007362 could suppress the miR-493 expression and elevate the MCP-1 expression, and miR-493 was shown to respectively target AC007362 and MCP-1. Moreover, shear stress in HUVECs led to the down-regulated DNA methyltransferase 1 (DNMT1), as well as the decreased DNA methylation level of AC007362 promoter. Similar results were also observed in ruptured IA tissues when compared with unruptured IA tissues. In conclusion, this study presented a deep insight into the operation of the regulatory network of AC007362, miR-493 and MCP-1 upon shear stress. Under shear stress, the expression of AC007362 was enhanced by the inhibited promoter DNA methylation, while the expression of MCP-1 was enhanced by sponging the expression of miR-493. 相似文献
96.
97.
Plant Ecology - Seed germination and seedling recruitment are among the most critical stages for plant population persistence and development, which may be influenced by habitat fragmentation and... 相似文献
98.
Zhang M. Zhang J. Jiao R. T. Yang X. E. Ji D. W. 《Russian Journal of Plant Physiology》2021,68(6):1115-1124
Russian Journal of Plant Physiology - Hyperaccumulating ecotype (HE) of Sedum alfredii Hance is a Zn/Cd hyperaccumulator, which can accumulate Zn in shoot up to 2% of dry weight, understanding the... 相似文献
99.
The association of the FTO gene with obesity has been implicated in various human populations. The FTO gene is also most likely involved in the regulation of energy balance and feed intake. Here, the FTO gene was studied as a candidate gene for fatness and growth rate traits in pigs. The amino acid sequence of the FTO gene showed high conservation among human, pig, and other important domestic animals. Twelve variants including ten SNPs and two indels were detected, and then five SNPs within different genomic regions were genotyped in the ISU Berkshire × Yorkshire pig resource family. The linkage disequilibrium analyses revealed that most of these FTO variants were not in strong LD with each other. The SNPs c.46–139A > T within intron 1 and a synonymous mutation c.594C > G (Ala198Ala) within exon 3 had significant (P < 0.01) associations with average daily gain on test and total lipid percentage in muscle, respectively. Five major haplotypes were identified and the subsequent association analyses suggested that haplotype 2 (-CTTGG-) was the most favorable for increased growth rate, while haplotype 1 (-CTACG-) was unfavorably associated with intramuscular fatness traits. 相似文献
100.
Yuexin Ma Zhiming Liu Zhiping Yang Ming Li Jiao Liu Jian Song 《Fish & shellfish immunology》2013,34(1):66-73
A feeding experiment was conducted to determine effects of Hanseniaspora opuntiae C21 on immune response and disease resistance against Vibrio splendidus infection in juvenile sea cucumbers Apostichopus japonicus. Sea cucumbers were fed with either diets containing C21 at 104, 105 and 106 CFU g?1 feed or a control diet for 30–50 days, respectively. After feeding for 30 days and 45 days, five sea cucumbers from each tank were sampled for immunological analyses. Results indicated that C21 significantly improved the phagocytic activity in coelomocytes of sea cucumbers (P < 0.05). Moreover, C21 administration significantly enhanced lysozyme (LSZ), phenoloxidase activity (PO), total nitric oxide synthase (T-NOS), superoxide dismutase (SOD), alkaline phosphatase (AKP) and acid phosphatase (ACP) activities in coelomic fluid, and LSZ, T-NOS, AKP and ACP activities in coelomocytes lysate supernatant (CLS) of sea cucumbers (P < 0.05). After feeding for 45 days, 10 sea cucumbers from each dose group were challenged with V. splendidus NB13. Cumulative incidence and mortality of sea cucumbers fed with C21 were found to be lower than those of control group. After feeding for 50 days, sea cucumbers in 104 CFU g?1 C21 treatment and control tanks were subjected to acute salinity changes (from 30 to 20) for 24 h in the laboratory, and the immunological parameters were measured to evaluate the immune capacities of the A. japonicus. Phagocytic, LAZ and T-NOS activities of C21-treated group were higher than those of control group, indicating that salinity stress tolerance of sea cucumber was enhanced by C21. The present results showed that a diet supplemented with C21 could stimulate the immune system of juvenile A. japonicus thus enhancing their resistance against V. splendidus. 相似文献