全文获取类型
收费全文 | 21966篇 |
免费 | 1981篇 |
国内免费 | 2903篇 |
出版年
2024年 | 61篇 |
2023年 | 304篇 |
2022年 | 682篇 |
2021年 | 1112篇 |
2020年 | 867篇 |
2019年 | 1038篇 |
2018年 | 984篇 |
2017年 | 749篇 |
2016年 | 956篇 |
2015年 | 1532篇 |
2014年 | 1723篇 |
2013年 | 1755篇 |
2012年 | 2253篇 |
2011年 | 1987篇 |
2010年 | 1238篇 |
2009年 | 1152篇 |
2008年 | 1300篇 |
2007年 | 1139篇 |
2006年 | 1029篇 |
2005年 | 857篇 |
2004年 | 730篇 |
2003年 | 621篇 |
2002年 | 483篇 |
2001年 | 292篇 |
2000年 | 289篇 |
1999年 | 258篇 |
1998年 | 196篇 |
1997年 | 186篇 |
1996年 | 148篇 |
1995年 | 131篇 |
1994年 | 133篇 |
1993年 | 78篇 |
1992年 | 88篇 |
1991年 | 75篇 |
1990年 | 52篇 |
1989年 | 46篇 |
1988年 | 36篇 |
1987年 | 39篇 |
1986年 | 28篇 |
1985年 | 38篇 |
1984年 | 20篇 |
1983年 | 13篇 |
1982年 | 23篇 |
1981年 | 13篇 |
1980年 | 9篇 |
1978年 | 10篇 |
1976年 | 12篇 |
1975年 | 12篇 |
1973年 | 10篇 |
1972年 | 8篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
Tao Tian Danhua Yao Lei Zheng Zhiyuan Zhou Yantao Duan Bin Liu Pengfei Wang Yousheng Li 《Cell death & disease》2020,11(12)
Previously, we confirmed that sphingosine kinase 1 (SphK1) inhibition improves sepsis-associated liver injury. High-mobility group box 1 (HMGB1) translocation participates in the development of acute liver failure. However, little information is available on the association between SphK1 and HMGB1 translocation during sepsis-associated liver injury. In the present study, we aimed to explore the effect of SphK1 inhibition on HMGB1 translocation and the underlying mechanism during sepsis-associated liver injury. Primary Kupffer cells and hepatocytes were isolated from SD rats. The rat model of sepsis-associated liver damage was induced by intraperitoneal injection with lipopolysaccharide (LPS). We confirmed that Kupffer cells were the cells primarily secreting HMGB1 in the liver after LPS stimulation. LPS-mediated HMGB1 expression, intracellular translocation, and acetylation were dramatically decreased by SphK1 inhibition. Nuclear histone deacetyltransferase 4 (HDAC4) translocation and E1A-associated protein p300 (p300) expression regulating the acetylation of HMGB1 were also suppressed by SphK1 inhibition. HDAC4 intracellular translocation has been reported to be controlled by the phosphorylation of HDAC4. The phosphorylation of HDAC4 is modulated by CaMKII-δ. However, these changes were completely blocked by SphK1 inhibition. Additionally, by performing coimmunoprecipitation and pull-down assays, we revealed that SphK1 can directly interact with CaMKII-δ. The colocalization of SphK1 and CaMKII-δ was verified in human liver tissues with sepsis-associated liver injury. In conclusion, SphK1 inhibition diminishes HMGB1 intracellular translocation in sepsis-associated liver injury. The mechanism is associated with the direct interaction of SphK1 and CaMKII-δ.Subject terms: Hepatotoxicity, Sepsis 相似文献
2.
3.
Fang Chang An Yan Li-Na Zhao Wei-Hua Wu Zhenbiao Yang 《植物学报(英文版)》2007,49(8):1261-1270
A tip-focused Ca^2+ gradient is tightly coupled to polarized pollen tube growth, and tip-localized influxes of extracellular Ca^2+ are required for this process. However the molecular identity and regulation of the potential Ca^2+ channels remains elusive. The present study has implicated CNGC18 (cyclic nucleotide-gated channel 18) in polarized pollen tube growth, because its overexpression induced wider and shorter pollen tubes. Moreover, CNGC18 overexpression induced depolarization of pollen tube growth was suppressed by lower extracellular calcium ([Ca^2+]ex). CNGC18-yellow fluorescence protein (YFP) was preferentially localized to the apparent post-Golgi vesicles and the plasma membrane (PM) in the apex of pollen tubes. The PM localization was affected by tip-localized ROP1 signaling. Expression of wild type ROP1 or an active form of ROP1 enhanced CNGC18-YFP localization to the apical region of the PM, whereas expression of RopGAP1 (a ROP1 deactivator) blocked the PM localization. These results support a role for PM-Iocalized CNGC18 in the regulation of polarized pollen tube growth through its potential function in the modulation of calcium influxes. 相似文献
4.
5.
Many animals exhibit different behaviors in different seasons. The photoperiod can have effects on migration, breeding, fur growth, and other processes. The cyclic growth of the fur and feathers of some species of mammals and birds, respectively, is stimulated by the photoperiod as a result of hormone-dependent regulation of the nervous system. To further examine this phenomenon, we evaluated the Arbas Cashmere goat (Capra hircus), a species that is often used in this type of research. The goats were exposed to an experimentally controlled short photoperiod to study the regulation of cyclic cashmere growth. Exposure to a short photoperiod extended the anagen phase of the Cashmere goat hair follicle to increase cashmere production. Assessments of tissue sections indicated that the short photoperiod significantly induced cashmere growth. This conclusion was supported by a comparison of the differences in gene expression between the short photoperiod and natural conditions using gene chip technology. Using the gene chip data, we identified genes that showed altered expression under the short photoperiod compared to natural conditions, and these genes were found to be involved in the biological processes of hair follicle growth, structural composition of the hair follicle, and the morphogenesis of the surrounding skin appendages. Knowledge about differences in the expression of these genes as well as their functions and periodic regulation patterns increases our understanding of Cashmere goat hair follicle growth. This study also provides preliminary data that may be useful for the development of an artificial method to improve cashmere production by controlling the light cycle, which has practical significance for livestock breeding. 相似文献
6.
7.
8.
Ying Jin Dan Long Juan Li Ruichao Yu Yueming Song Jie Fang Xi Yang Shu Zhou Shishu Huang Zhihe Zhao 《Journal of cellular physiology》2019,234(9):14838-14851
Bone and tooth, fundamental parts of the craniofacial skeleton, are anatomically and developmentally interconnected structures. Notably, pathological processes in these tissues underwent together and progressed in multilevels. Extracellular vesicles (EVs) are cell-released small organelles and transfer proteins and genetic information into cells and tissues. Although EVs have been identified in bone and tooth, particularly EVs have been identified in the bone formation and resorption, the concrete roles of EVs in bone and tooth development and diseases remain elusive. As such, we review the recent progress of EVs in bone and tooth to highlight the novel findings of EVs in cellular communication, tissue homeostasis, and interventions. This will enhance our comprehension on the skeletal biology and shed new light on the modulation of skeletal disorders and the potential of genetic treatment. 相似文献
9.
10.