全文获取类型
收费全文 | 131100篇 |
免费 | 3236篇 |
国内免费 | 2768篇 |
专业分类
137104篇 |
出版年
2024年 | 87篇 |
2023年 | 443篇 |
2022年 | 1097篇 |
2021年 | 1762篇 |
2020年 | 1225篇 |
2019年 | 1504篇 |
2018年 | 12973篇 |
2017年 | 11417篇 |
2016年 | 8803篇 |
2015年 | 3078篇 |
2014年 | 3119篇 |
2013年 | 3324篇 |
2012年 | 7662篇 |
2011年 | 15689篇 |
2010年 | 13765篇 |
2009年 | 9761篇 |
2008年 | 11766篇 |
2007年 | 13115篇 |
2006年 | 1906篇 |
2005年 | 1925篇 |
2004年 | 2214篇 |
2003年 | 2070篇 |
2002年 | 1595篇 |
2001年 | 983篇 |
2000年 | 745篇 |
1999年 | 639篇 |
1998年 | 344篇 |
1997年 | 349篇 |
1996年 | 315篇 |
1995年 | 274篇 |
1994年 | 279篇 |
1993年 | 222篇 |
1992年 | 314篇 |
1991年 | 295篇 |
1990年 | 192篇 |
1989年 | 161篇 |
1988年 | 131篇 |
1987年 | 145篇 |
1986年 | 108篇 |
1985年 | 94篇 |
1984年 | 71篇 |
1983年 | 70篇 |
1982年 | 51篇 |
1981年 | 37篇 |
1980年 | 42篇 |
1979年 | 44篇 |
1975年 | 40篇 |
1974年 | 34篇 |
1972年 | 272篇 |
1971年 | 290篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
961.
Shaochen Fan Huasong Gao Wei Ji Fengwei Zhu Lingzheng Sun Yuankun Liu Siming Zhang Yanran Xu Yaohua Yan Yilu Gao 《Journal of cellular physiology》2020,235(2):1769-1779
Although much progress has been made in the treatment of gliomas, the prognosis for patients with gliomas is still very poor. Stem cell-based therapies may be promising options for glioma treatment. Recently, many studies have reported that umbilical cord-derived mesenchymal stromal/stem cells (UC-MSCs) are ideal gene vehicles for tumor gene therapy. Interleukin 24 (IL-24) is a pleiotropic immunoregulatory cytokine that has an apoptotic effect on many kinds of tumor cells and can inhibit the growth of tumors specifically without damaging normal cells. In this study, we investigated UC-MSCs as a vehicle for the targeted delivery of IL-24 to tumor sites. UC-MSCs were transduced with lentiviral vectors carrying green fluorescent protein (GFP) or IL-24 complementary DNA. The results indicated that UC-MSCs could selectively migrate to glioma cells in vitro and in vivo. Injection of IL-24-UC-MSCs significantly suppressed tumor growth of glioma xenografts. The restrictive efficacy of IL-24-UC-MSCs was associated with the inhibition of proliferation as well as the induction of apoptosis in tumor cells. These findings indicate that UC-MSC-based IL-24 gene therapy may be able to suppress the growth of glioma xenografts, thereby suggesting possible future therapeutic use in the treatment of gliomas. 相似文献
962.
Zixi Chen Qiaoli Liu Zhaowei Zhu Fenfen Xiang Rong Wu Xiangdong Kang 《Journal of cellular physiology》2020,235(1):513-525
Evidence indicates that inflammatory response is significant during the physiological process of human parturition; however, the specific signaling pathway that triggers inflammation is undefined. Toll-like receptors (TLRs) are key upstream gatekeepers that control inflammatory activation before preterm delivery. Our previous study showed that TLR4 expression was significantly increased in human pregnancy tissue during preterm and term labor. Therefore, we explore whether TLR4 plays a role in term labor by initiating inflammatory responses, therefore promoting uterine activation. The results showed that expression of TLR4, interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), CC chemokine ligand 2 (CCL-2), and uterine contraction-associated proteins (CAPs) was upregulated in the human and mice term labor (TL) group compared with the not-in-labor (TNL) group, and the TLR4 level positively correlated with CAP expression. In pregnant TLR4-knockout (TLR4−/−) mice, gestation length was extended by 8 hr compared with the wild-type group, and the expression of IL-1β, IL-6, TNF-α, CCL-2, and CAPs was decreased in TLR4−/− mice. Furthermore, nuclear factor-κB (NF-κB) and P38MAPK activation is involved in the initiation of labor but was inhibited in TLR4−/− mice. In uterine smooth muscle cells, the expression of inflammatory cytokines and CAPs decreased when the NF-κB and P38MAPK pathway was inhibited. Our data suggest that TLR4 is a key factor in regulating the inflammatory response that drives uterine activation and delivery initiation via activating the NF-κB/P38MAPK pathway. 相似文献
963.
Wei Gao Chao-Qun Qi Mao-Guo Feng Peng Yang Li Liu Shu-Hong Sun 《Journal of cellular physiology》2020,235(10):6684-6696
Long noncoding RNAs (lncRNAs) have been shown to have critical regulatory roles in tumorigenesis. lncRNA LINC01561 (LINC01561) is a newly identified tumor-related lncRNA and its dysregulation has been demonstrated in several tumors. However, whether LINC01561 is involved in the progression of non-small-cell lung carcinoma (NSCLC) and its underlying mechanisms remain unknown. In this study, we first provided evidence that LINC01561 expressions were distinctly upregulated in NSCLC tissues and cell lines. Combining with bioinformatics assays and mechanism experiments, our group demonstrated that LINC01561 was activated by SOX2 in NSCLC. Clinical research revealed that upregulation of LINC01561 was related to poorer clinicopathologic features and shorter survival time. Functionally, suppression of LINC01561 exhibited tumor-suppressive functions through impairing cell proliferation, migration, and invasion as well as inducing apoptosis. Moreover, we verified that LINC01561 could directly bind to miR-760, isolating miR-760 from its target gene SHC SH2 domain-binding protein 1 (SHCBP1). We also found that SHCBP1 was lowly expressed in NSCLC and served as a tumor promoter. A functional study indicated that LINC01561 regulated SHCBP1 expression by competitively binding to miR-760. In summary, our findings indicated that SOX2-induced overexpression of LINC01561 promoted the proliferation and metastasis by acting as a competing endogenous RNA to modulate SHCBP1 by sponging miR-760. 相似文献
964.
Jingwen Li Jing Zou Xiaoyue Wan Chunyan Sun Zhangbo Chu Yu Hu 《Journal of cellular physiology》2020,235(11):7681-7695
Despite the administration of new effective drugs in recent years, relapse and drug resistance are still the main obstacles in multiple myeloma (MM) treatment, making MM an incurable disease. To overcome drug resistance in MM, it is critical to understand the underlying mechanisms of malfunctioning gene expression and develop novel targeted therapies. During the past few decades, with the discovery and characterization of noncoding RNAs (ncRNAs), the landscape of dysregulated ncRNAs of cancers as well as their biological and pathobiological functions in tumorigenesis and drug resistance have been recognized. Studies about ncRNAs improved the understanding of variations of drug response among individuals at a level distinguished from genetic polymorphism, and provided with new orientations for targeted therapies. In this review, we will summarize the emerging impact and underlying molecular mechanisms of the most relevant classes of ncRNAs in drug resistance of MM, and discuss the potential as well as strategies of treating ncRNAs as therapeutic targets. 相似文献
965.
Xuefei Yu Ying Sun Kaican Cai Hongfeng Yu Difu Zhou Di Lu Sherman Xuegang Xin 《Bioelectromagnetics》2020,41(2):148-155
The dielectric properties of normal and tumor human tissues have been widely reported in recent years. However, the dielectric properties of intrathoracic lymph nodes (LNs) have not been reported. In this communication, we measured the dielectric properties (i.e., permittivity and conductivity) of ex vivo intrathoracic LNs obtained from lung cancer surgeries. Results show that the permittivity and conductivity of metastatic LNs are higher than those of normal LNs over the frequency range of 1 MHz–4 GHz. Statistically significant differences are observed at single specific frequencies (64, 128, 298, 433, and 915 MHz and 2.45 GHz). Our study provides the basic data to support future-related research and fills the research gap on the dielectric properties of LNs in the lungs. Bioelectromagnetics. 2020;41:148–155. © 2020 Bioelectromagnetics Society. 相似文献
966.
967.
Amelie Croset Fabrice P. Cordelières Nathalie Berthault Cyril Buhler Jian-Sheng Sun Maria Quanz Marie Dutreix 《Nucleic acids research》2013,41(15):7344-7355
One of the major early steps of repair is the recruitment of repair proteins at the damage site, and this is coordinated by a cascade of modifications controlled by phosphatidylinositol 3-kinase-related kinases and/or poly (ADP-ribose) polymerase (PARP). We used short interfering DNA molecules mimicking double-strand breaks (called Dbait) or single-strand breaks (called Pbait) to promote DNA-dependent protein kinase (DNA-PK) and PARP activation. Dbait bound and induced both PARP and DNA-PK activities, whereas Pbait acts only on PARP. Therefore, comparative study of the two molecules allows analysis of the respective roles of the two signaling pathways: both recruit proteins involved in single-strand break repair (PARP, XRCC1 and PCNA) and prevent their recruitment at chromosomal damage. Dbait, but not Pbait, also inhibits recruitment of proteins involved in double-strand break repair (53BP1, NBS1, RAD51 and DNA-PK). By these ways, Pbait and Dbait disorganize DNA repair, thereby sensitizing cells to various treatments. Single-strand breaks repair inhibition depends on direct trapping of the main proteins on both molecules. Double-strand breaks repair inhibition may be indirect, resulting from the phosphorylation of double-strand breaks repair proteins and chromatin targets by activated DNA-PK. The DNA repair inhibition by both molecules is confirmed by their synthetic lethality with BRCA mutations. 相似文献
968.
969.
Wenjing Song Huwei Sun Jiao Li Xianpo Gong Shuangjie Huang Xudong Zhu Yali Zhang Guohua Xu 《Annals of botany》2013,112(7):1383-1393
Background and Aims
Although ammonium (NH4+) is the preferred form of nitrogen over nitrate (NO3−) for rice (Oryza sativa), lateral root (LR) growth in roots is enhanced by partial NO3− nutrition (PNN). The roles of auxin distribution and polar transport in LR formation in response to localized NO3− availability are not known.Methods
Time-course studies in a split-root experimental system were used to investigate LR development patterns, auxin distribution, polar auxin transport and expression of auxin transporter genes in LR zones in response to localized PNN in ‘Nanguang’ and ‘Elio’ rice cultivars, which show high and low responsiveness to NO3−, respectively. Patterns of auxin distribution and the effects of polar auxin transport inhibitors were also examined in DR5::GUS transgenic plants.Key Results
Initiation of LRs was enhanced by PNN after 7 d cultivation in ‘Nanguang’ but not in ‘Elio’. Auxin concentration in the roots of ‘Nanguang’ increased by approx. 24 % after 5 d cultivation with PNN compared with NH4+ as the sole nitrogen source, but no difference was observed in ‘Elio’. More auxin flux into the LR zone in ‘Nanguang’ roots was observed in response to NO3− compared with NH4+ treatment. A greater number of auxin influx and efflux transporter genes showed increased expression in the LR zone in response to PNN in ‘Nanguang’ than in ‘Elio’.Conclusions
The results indicate that higher NO3− responsiveness is associated with greater auxin accumulation in the LR zone and is strongly related to a higher rate of LR initiation in the cultivar ‘Nanguang’. 相似文献970.
Yibo Wang Jinxing Chen Yu Zhang Lv Bin Kai Sun Weifeng Yu Jibin Liu Channa Zhang Haiqing Shen Zhihui Hou Fangfang Yu Rutai Hui 《Human genetics》2013,132(1):29-37
VKORC1 genetic polymorphisms affect warfarin dose response, aortic calcification, and the susceptibility of coronary artery disease as shown in our previous study. Little is known regarding the association of VKORC1 polymorphisms with coronary artery calcification (CAC) and the role of CAC in the association with coronary artery disease (CAD). Due to a natural haplotype block in the VKORC1 gene in Chinese, polymorphism rs2359612 was analyzed in a case–control study and a prospective study. The case–control study included 464 CAD patients with non-calcified plaque (NCP), 562 CAD patients with mixed calcified plaque (MCP), 492 subjects with calcified plaque (CP), and 521 controls. The rs2359612C was only associated with increased risk of MCP, the CAD in the presence of CAC; the odds ratio was 1.397 (95 % CI 1.008–1.937, P < 0.05), which was replicated in the second independent population. On the contrary, a negative correlation was observed between rs2359612 and log-transformed Agatston score, and rs2359612 was negatively associated with the number of calcified vessels. Moreover, in a prospective study including 849 CAD patients undergoing revascularization, rs2359612C predicted a higher incidence of cardiovascular events in MCP subgroup; the relative risk was 1.435 (95 % CI 1.008–2.041, P = 0.045), which was not observed in the NCP subgroup. We conclude that the rs2359612C was associated with a higher risk of CAD in the presence of CAC and a higher incidence of cardiovascular events in CAD patients with CAC, but a lower coronary calcification. VKORC1 polymorphisms may be associated with the endophenotype of CAD, calcification-related atherosclerosis. 相似文献