全文获取类型
收费全文 | 15468篇 |
免费 | 1408篇 |
国内免费 | 1481篇 |
出版年
2024年 | 28篇 |
2023年 | 240篇 |
2022年 | 596篇 |
2021年 | 972篇 |
2020年 | 658篇 |
2019年 | 779篇 |
2018年 | 704篇 |
2017年 | 509篇 |
2016年 | 701篇 |
2015年 | 1088篇 |
2014年 | 1262篇 |
2013年 | 1190篇 |
2012年 | 1520篇 |
2011年 | 1207篇 |
2010年 | 767篇 |
2009年 | 668篇 |
2008年 | 777篇 |
2007年 | 675篇 |
2006年 | 554篇 |
2005年 | 485篇 |
2004年 | 371篇 |
2003年 | 349篇 |
2002年 | 246篇 |
2001年 | 266篇 |
2000年 | 189篇 |
1999年 | 204篇 |
1998年 | 116篇 |
1997年 | 131篇 |
1996年 | 131篇 |
1995年 | 120篇 |
1994年 | 124篇 |
1993年 | 76篇 |
1992年 | 87篇 |
1991年 | 104篇 |
1990年 | 67篇 |
1989年 | 61篇 |
1988年 | 36篇 |
1987年 | 35篇 |
1986年 | 23篇 |
1985年 | 40篇 |
1984年 | 21篇 |
1983年 | 28篇 |
1982年 | 12篇 |
1981年 | 9篇 |
1980年 | 9篇 |
1978年 | 9篇 |
1977年 | 9篇 |
1974年 | 9篇 |
1973年 | 10篇 |
1971年 | 12篇 |
排序方式: 共有10000条查询结果,搜索用时 109 毫秒
821.
Although superhydrophobic materials have attracted much research interest in anti-icing,some controversy still exists.In this research,we report a cost-effective method used to verify the contribution of area fraction to ice adhesion strength.We tried to partially-embed siliea nanopnarticles into microscale fabrics of a commercial polyamide mesh.Then,the area fraction could be determined by altering the mesh size.Generally,the ice adhesion strength decreases as the area fraction decreases.An ice adhesion strength of~1.9 kPa and a delayed freezing time of~1048 s can be obtained.We attribute the low ice adhesion strength to the combination of superhydro-phobicity and stress concentration.The superhydrophobicity prohibits the water from penetrating into the voids of the meshes,and the small actual contact area leads to stress concentration which promotes interfacial crack propagation.Moreover,our superhydrophobic mesh simultaneously exhibis a micro-nano hierarchical structure and a partally-cmbedded structure.Therefore,the as-prepared superhydrophobic mesh retained the ieephobicity after 20 icingldeicing cycles,and maintained its superhydrophobicity even afier 60 sandpaper-abrasion cycles and a 220"C thermal treatment. 相似文献
822.
Yuxian Zhang Jianlan Xie Diangang Liu Shengtao Zhu Shutian Zhang 《Genetics and molecular biology》2022,45(1)
Our present study aims to investigate the value of LRRN4 in the progression and prognosis of COAD patients. All COAD and adjacent sample data was downloaded from TCGA database. Survival analysis was performed according to Kaplan-Meier method. The real-time quantitative PCR and immunohistochemistry analysis were conducted for validation in cell lines and tissues. The GSEA was conducted to find functional KEGG pathways. Multivariate Cox regression proportional hazard mode was used to determine whether LRRN4 expression was an independent prognostic factor. The LRRN4 expression in COAD samples were significantly higher than that in adjacent samples, which was consistent with our experiments in cell lines and tissues. Along with the increase of TNM Stage, LRRN4 expression had an increasing tendency. The COAD patients with high LRRN4 expression showed undesirable prognoses. Additionally, the TGF-β signaling pathway, WNT signaling pathway and other 25 pathways were significantly activated in the high LRRN4 expression group. In conclusion, high LRRN4 expression was closely related to the onset of COAD and it was a poor prognostic factor for COAD patients.Keywords: Colon adenocarcinoma, LRRN4, prognosis, biomarker 相似文献
823.
Xin Xie Jingwen Lv Wei Zhu Chao Tian Jingfeng Li Jiajia Liu Hua Zhou Chunyang Sun Zongfeng Hu Xiaopeng Li 《Translational oncology》2022,15(1)
Cancer immunotherapy is a new therapeutic strategy for cancer treatment that targets tumors by improving or restoring immune system function. Therapies targeting immune checkpoint molecules have exerted potent anti-tumor effects and prolonged the overall survival rate of patients. However, only a small number of patients benefit from the treatment. Oncolytic viruses exert anti-tumor effects by regulating the tumor microenvironment and affecting multiple steps of tumor immune circulation. In this study, we engineered two oncolytic viruses that express mouse anti-PD-1 antibody (VT1093M) or mouse IL-12 (VT1092M). We found that both oncolytic viruses showed significant anti-tumor effects in a murine CT26 colon adenocarcinoma model. Importantly, the intratumoral combined injection with VT1092M and VT1093M inhibited growth of the primary tumor, prevented growth of the contralateral untreated tumor, produced a vaccine-like response, activated antigen-specific T cell responses and prolonged the overall survival rate of mice. These results indicate that combination therapy with the engineered oncolytic virus may represent a potent immunotherapy strategy for cancer patients, especially those resistant to PD-1/PD-L1 blockade therapy. 相似文献
824.
825.
Kuan Lai Wenjing Zhang Songshan Li Zhiwen Zhang Shuangde Xie Meinian Xu Changxing Li Kang Zeng 《Acta biochimica et biophysica Sinica》2021,(4):438-445
Pemphigus vulgaris (PV) is a chronic and potentially life-threatening autoimmune blistering disease.Aberrant mTOR pathway activity is involved in many autoimmun... 相似文献
826.
Zhiling Zhou Jiaxin Zhan Qiong Luo Xinghua Hou Shuxia Wang Dingzhang Xiao Zhi Xie Haidan Liang Shuguang Lin Meng Zheng 《Cell death & disease》2022,13(2)
Metastatic tumors are mainly composed of neoplastic cells escaping from the primary tumor and inflammatory cells egressing from bone marrow. Cancer cell and inflammatory cell are remained in the state of immaturity during migration to distant organs. Here, we show that ADRB3 is crucial in cell mobilization and differentiation. Immunohistochemistry revealed ADRB3 expression is significantly more frequent in breast cancer tissues than in adjacent noncancerous tissues (92.1% vs. 31.5%). Expression of ADRB3 correlated with malignant degree, TNM stage and poor prognosis. Moreover, ADRB3 expression was markedly high in activated disseminated tumor cells, myeloid-derived suppressor cells (MDSCs), lymphocytes and neutrophil extracellular traps of patients. Importantly, ADRB3 promoted the expansion of MDSC through stimulation of bone marrow mobilization and inhibiting of the differentiation of immature myeloid cells. Furthermore, ADRB3 promoted MCF-7 cells proliferation and inhibited transdifferentiation into adipocyte-like cell by activating mTOR pathway. Ultimately, the MDSC-deficient phenotype of ADRB3 -/- PyMT mice was associated with impairment of mammary tumorigenesis and reduction in pulmonary metastasis. Collectively, ADRB3 promotes metastasis by inducing mobilization and inhibiting differentiation of both breast cancer cells and MDSCs.Subject terms: Breast cancer, Breast cancer 相似文献
827.
Mengmeng Jiang Hai Xie Chaoyang Zhang Tianqin Wang Haibin Tian Lixia Lu JingYing Xu GuoTong Xu Lin Liu Jingfa Zhang 《Journal of cellular and molecular medicine》2022,26(4):1229
The concept of diabetic retinopathy (DR) has been extended from microvascular disease to neurovascular disease in which microglia activation plays a remarkable role. Fractalkine (FKN)/CX3CR1 is reported to regulate microglia activation in central nervous system diseases. To characterize the effect of FKN on microglia activation in DR, we employed streptozotocin‐induced diabetic rats, glyoxal‐treated R28 cells and hypoxia‐treated BV2 cells to mimic diabetic conditions and explored retinal neuronal apoptosis, reactive oxygen species (ROS), as well as the expressions of FKN, Iba‐1, TSPO, NF‐κB, Nrf2 and inflammation‐related cytokines. The results showed that FKN expression declined with diabetes progression and in glyoxal‐treated R28 cells. Compared with normal control, retinal microglia activation and inflammatory factors surged in both diabetic rat retinas and hypoxia‐treated microglia, which was largely dampened by FKN. The NF‐κB and Nrf2 expressions and intracellular ROS were up‐regulated in hypoxia‐treated microglia compared with that in normoxia control, and FKN significantly inhibited NF‐κB activation, activated Nrf2 pathway and decreased intracellular ROS. In conclusion, the results demonstrated that FKN deactivated microglia via inhibiting NF‐κB pathway and activating Nrf2 pathway, thus to reduce the production of inflammation‐related cytokines and ROS, and protect the retina from diabetes insult. 相似文献
828.
Zhijing Xie Xin Sun Johannes Lux TingWen Chen Mikhail Potapov Donghui Wu Stefan Scheu 《Ecology and evolution》2022,12(2)
Altitudinal changes in the diversity of plants and animals have been well documented; however, soil animals received little attention in this context and it is unclear whether their diversity follows general altitudinal distribution patterns. Changbai Mountain is one of few well‐conserved mountain regions comprising natural ecosystems on the Eurasian continent. Here, we present a comprehensive analysis of the diversity and community composition of Collembola along ten altitudinal sites representing five vegetation types from forest to alpine tundra. Among 7834 Collembola individuals, 84 morphospecies were identified. Species richness varied marginally significant with altitude and generally followed a unimodal relationship with altitude. By contrast, the density of Collembola did not change in a consistent way with altitude. Collembola communities changed gradually with altitude, with local habitat‐related factors (soil and litter carbon‐to‐nitrogen ratio, litter carbon content, and soil pH) and climatic variables (precipitation seasonality) identified as major drivers of changes in Collembola community composition. Notably, local habitat‐related factors explained more variation in Collembola assemblages than climatic variables. The results suggest that local habitat‐related factors including precipitation and temperature are the main drivers of changes in Collembola communities with altitude. Specifically, soil and litter carbon‐to‐nitrogen ratio correlated positively with Collembola communities at high altitudes, whereas soil pH correlated positively at low altitudes. This documents that altitudinal gradients provide unique opportunities for identifying factors driving the community composition of not only above‐ but also belowground invertebrates. 相似文献
829.
830.
Xuefei Zhu Jingwei Xue Xing Jiang Yamin Gong Congwen Gao Ting Cao Qian Li Lulu Bai Yuwei Li Gaixia Xu Bin Peng Xingzhi Xu 《Nucleic acids research》2022,50(3):1517
Expression of the E3 ligase TRIM21 is increased in a broad spectrum of cancers; however, the functionally relevant molecular pathway targeted by TRIM21 overexpression remains largely unknown. Here, we show that TRIM21 directly interacts with and ubiquitinates CLASPIN, a mediator for ATR-dependent CHK1 activation. TRIM21-mediated K63-linked ubiquitination of CLASPIN counteracts the K6-linked ubiquitination of CLASPIN which is essential for its interaction with TIPIN and subsequent chromatin loading. We further show that overexpression of TRIM21, but not a TRIM21 catalytically inactive mutant, compromises CHK1 activation, leading to replication fork instability and tumorigenesis. Our findings demonstrate that TRIM21 suppresses CHK1 activation by preferentially targeting CLASPIN for K63-linked ubiquitination, providing a potential target for cancer therapy. 相似文献