全文获取类型
收费全文 | 1899篇 |
免费 | 145篇 |
国内免费 | 107篇 |
专业分类
2151篇 |
出版年
2024年 | 6篇 |
2023年 | 28篇 |
2022年 | 87篇 |
2021年 | 110篇 |
2020年 | 62篇 |
2019年 | 77篇 |
2018年 | 73篇 |
2017年 | 51篇 |
2016年 | 86篇 |
2015年 | 123篇 |
2014年 | 130篇 |
2013年 | 137篇 |
2012年 | 167篇 |
2011年 | 128篇 |
2010年 | 91篇 |
2009年 | 73篇 |
2008年 | 71篇 |
2007年 | 85篇 |
2006年 | 65篇 |
2005年 | 72篇 |
2004年 | 60篇 |
2003年 | 66篇 |
2002年 | 51篇 |
2001年 | 38篇 |
2000年 | 20篇 |
1999年 | 35篇 |
1998年 | 17篇 |
1997年 | 8篇 |
1996年 | 11篇 |
1995年 | 16篇 |
1994年 | 16篇 |
1993年 | 10篇 |
1992年 | 11篇 |
1991年 | 15篇 |
1990年 | 6篇 |
1989年 | 9篇 |
1988年 | 4篇 |
1987年 | 4篇 |
1986年 | 9篇 |
1985年 | 2篇 |
1984年 | 4篇 |
1983年 | 5篇 |
1980年 | 1篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 2篇 |
1970年 | 2篇 |
排序方式: 共有2151条查询结果,搜索用时 15 毫秒
71.
72.
XiuFang Weng ZhiHui Liang XiaoLing Lu MaoHua Zhong ShengJun Lu CaiE Zhang Jing Deng XiongWen Wu FeiLi Gong 《中国科学:生命科学英文版》2007,50(2):203-211
The role of the bound peptide in alloreactive T-cell recognition is controversial, ranging from pep-tide-independent to peptide-specific recognition of alloreactive T-cells. The aim of this study is to find the evidence that there exist peptide/MHC complex (pMHC)-specific CTLs among alloreactive T cells generated with long-term mixed lymphocytes culture (LTMLC). A single pMHC was manipulated by loading the TAP-defective, HLA-A2 expressing T2 cells with a viral peptide (LMP2A426-434) or a self-peptide (Tyr369-377). The PBLs samples from 4 HLA-A2 positive (HLA-A2 ve) and 4 HLA-A2 negative (HLA-A2-ve) donors were included in this study. The HLA-A2 ve PBL co-cultured with the LMP2A426-434 pulsed T2 (T2/LMP) stands for the nominal T-cell response to a viral antigen, and the HLA-A2-ve PBLs co-cultured with the Tyr369-377 pulsed T2 (T2/Tyr) for alloreactive T-cell response to an allogeneic antigen. The specificity of the expanded CTLs after the LTMLC was detected by their specific cytotoxicity and binding ability to specific pMHC-tetramer. An HLA-A2 restricted, HIV peptide (Gag77-85)was included for control. The cultural bulk of HLA-A2 ve PBLs with the T2/LMP showed an elevated specific cytotoxicity against the T2/LMP compared to that against the T2/HIV (26.52%±3.72% vs 7.01%±0.87%, P<0.001), and an increased frequency of binding to LMP-tetramer compared to that binding to HIV-tetramer (0.98%±0.33% vs 0.05%±0.01%, P=0.0014). The cultural bulk of HLA-A2-ve PBLs with the T2/Tyr showed a more active cytotoxicity against the T2/Tyr than that against T2/HIV (28.07%±2.58% vs 6.87%±0.01 %, P<0.001), and a higher frequency of binding to the Tyr-tetramer than that binding to the HIV-tetramer (0.88%±0.3% vs 0.06%±0.03%, P=0.0018). Our results indicate that the LTMLC is able to expand the viral antigen-specific CTLs as well as allogeneic antigen-specific CTLs. A relatively large proportion of alloreactive CTLs should be pMHC-specific, i.e., the specificity of the alloreactive lines depends on both the bound peptide and the allotype of MHC. Our observations support the hypothesis that the cumulative effect of T cells specific to each peptide epitope could account for the strength and diversity of the alloresponse. The method using manipulated pMHC and the LTMLC to generate pMHC-specific, alloreactive CTLs is of potential importance for adoptive T-cell immunotherapy. 相似文献
73.
Yin Chun-yu Lu Hong-zhou Jiang Wei-ming Maria Pia De Pasquale Hu Yue-kai Pan Xiao-zhang Weng Xin-hua Richard T. D’Aquila Tang Yi-Wei 《中国病毒学》2007,22(3):212-217
Illegally paid blood donation was a risk factor for HIV acquisition exclusively in Henan and Hubei Provinces of China, and
not in Shanghai. Nucleotide sequences in the gag and env genes of HIV-1 were compared between isolates from Henan and Shanghai regions of China to test whether an expected higher
degree of a common source of infections from this unique blood donation transmission risk would be evident as decreased variation
among Henan isolates in an exploratory cross-sectional analysis. Among 38 isolates studied, 23 of 23 (100%) from Henan and
8 of 15 (54%) from Shanghai were subtype B. In addition, fewer sequence differences were found in gp41 of subtype B isolates
from Henan than from Shanghai isolates. Further studies with additional controls are therefore warranted to confirm the role
of the degree of a common source of infections in differences in HIV variation across populations.
Fundation items: The Vanderbilt-Meharry Center for AIDS Research (P30 AI 54999); R.T.D (R01 AI 29193); Start Fund of Ministry
of Education of China (for Hong-zhou LU, 2004BA719A10). 相似文献
74.
Guan Wang Zong-Jian Liu Xuan Liu Feng-Ge Liu Yan Li Yi-Bing Weng Jian-Xin Zhou 《Journal of cellular physiology》2019,234(11):20118-20127
This study aims to determine the feasibility of using oligodeoxynucleotides with unmethylated cytosine-guanine dinucleotide sequences (CpG ODN) as an immunity protection strategy for a mouse model of acute respiratory distress syndrome (ARDS). This is a prospective laboratory animal investigation. Twenty-week-old BALB/c mice in Animal research laboratory were randomized into groups. An ARDS model was induced in mice using lipopolysaccharides (LPSs). CpG ODN was intranasally and transrectally immunized before or after the 3rd and 7th days of establishing the ARDS model. Mice were euthanized on Day 7 after the second immunization. Then, retroorbital bleeding was carried out and the chest was rapidly opened to collect the trachea and tissues from both lungs for testing. CpG ODN significantly improved the pathologic impairment in mice lung, especially after the intranasal administration of 50 μg. This resulted in the least severe lung tissue injury. Furthermore, interleukin-6 (IL-6) and IL-8 concentrations were lower, which was second to mice treated with the rectal administration of 20 µg CpG ODN. In contrast, the nasal and rectal administration of CpG ODN in BALB/c mice before LPS immunization did not appear to exhibit any significant protective effects. The intranasal administration of CpG ODN may be a potential treatment approach to ARDS. More studies are needed to further determine the protective mechanism of CpG ODN. 相似文献
75.
Claassens Anders Rose Michael T. Van Zwieten Lukas Weng Zhe Rose Terry J. 《Plant and Soil》2019,439(1-2):393-404
Plant and Soil - Some studies have shown that an increasing atmospheric CO2 concentration reduces plant transpiration while others have demonstrated that it interacts with nutrients in soil to... 相似文献
76.
77.
Journal of Insect Behavior - Honey bees have three castes, drones, workers, and queens, that accomplish different tasks. In this research, we revealed the divergence in feeding behavior of drones... 相似文献
78.
79.
Yanan Ma Shanshan Wang Yongle Wu Bihan Liu Lei Li Wenjing Wang Honglei Weng Huiguo Ding 《Cell death & disease》2022,13(3)
Hepatic stellate cells (HSC) and hydrogen sulfide (H2S) both play important roles in the development of hepatocellar carcinoma (HCC). Whereas, in the microenvironment of HCC, whether HSC participate in regulating the biological process of HCC cells by releasing H2S remains elusive. In vitro, Flow cytometry (FCM), CCK-8, RNA-sequencing, Western blotting, RT-qPCR, immunofluorescence and ChIP assays were carried out in the HCC cells to investigate the effect of H2S on biological functions and JNK/JunB-TNFSF14 signaling pathway. Specimens from HCC patients were analyzed by RT-qPCR and Western blotting assays for evaluating the expression of TNFSF14 and CSE. Statistical analysis was used to analyze the correlation between TNFSF14 expression and clinical data of HCC patients. Based on the FCM and CCK-8 results, we found the LX-2 cells were able to induce HCC cells apoptosis through releasing H2S. RNA-sequencing, RT-qPCR, and Western blotting results showed that TNFSF14 gene was upregulated in both LX-2 and NaHS group. NaHS treated in HCC cells led to JNK/JunB signaling pathway activating and greater binding of p-JunB to its responsive elements on TNFSF14 promoter. Impairment of TNFSF14 induction alleviated LX-2 and NaHS induced apoptosis of HepG2 and PLC/PRF/5 cells. Furthermore, TNFSF14 expression in HCC tissues was lower than the adjacent tissue. HCC patients with low expression of TNFSF14 had higher malignant degree and poor prognosis. In summary, demonstration of the involvement of HSC-derived H2S in JNK/JunB mediated expression of TNFSF14 gene strongly indicates H2S palys an important role in the regulation of HCC apoptosis.Subject terms: Apoptosis, Liver cancer 相似文献
80.
Liping Meng Hui Lin Xingxiao Huang Jingfan Weng Fang Peng Shengjie Wu 《Cell death & disease》2022,13(1)
N6-methyladenosine (m6A) is one of the most important epigenetic regulation of RNAs, such as lncRNAs. However, the underlying regulatory mechanism of m6A in diabetic cardiomyopathy (DCM) is very limited. In this study, we sought to define the role of METTL14-mediated m6A modification in pyroptosis and DCM progression. DCM rat model was established and qRT-PCR, western blot, and immunohistochemistry (IHC) were used to detect the expression of METTL14 and TINCR. Gain-and-loss functional experiments were performed to define the role of METTL14-TINCR-NLRP3 axis in pyroptosis and DCM. RNA pulldown and RNA immunoprecipitation (RIP) assays were carried out to verify the underlying interaction. Our results showed that pyroptosis was tightly involved in DCM progression. METTL14 was downregulated in cardiomyocytes and hear tissues of DCM rat tissues. Functionally, METTL14 suppressed pyroptosis and DCM via downregulating lncRNA TINCR, which further decreased the expression of key pyroptosis-related protein, NLRP3. Mechanistically, METTL14 increased m6A methylation level of TINCR gene, resulting in its downregulation. Moreover, the m6A reader protein YTHDF2 was essential for m6A methylation and mediated the degradation of TINCR. Finally, TINCR positively regulated NLRP3 by increasing its mRNA stability. To conclude, our work revealed the novel role of METTL14-mediated m6A methylation and lncRNA regulation in pyroptosis and DCM, which could help extend our understanding the epigenetic regulation of pyroptosis in DCM progression.Subject terms: Cardiomyopathies, Endocrine system and metabolic diseases 相似文献