全文获取类型
收费全文 | 159篇 |
免费 | 14篇 |
国内免费 | 21篇 |
出版年
2023年 | 6篇 |
2022年 | 9篇 |
2021年 | 6篇 |
2020年 | 2篇 |
2019年 | 6篇 |
2018年 | 9篇 |
2017年 | 6篇 |
2016年 | 4篇 |
2015年 | 14篇 |
2014年 | 13篇 |
2013年 | 16篇 |
2012年 | 20篇 |
2011年 | 7篇 |
2010年 | 7篇 |
2009年 | 6篇 |
2008年 | 6篇 |
2007年 | 12篇 |
2006年 | 3篇 |
2005年 | 6篇 |
2004年 | 4篇 |
2003年 | 6篇 |
2002年 | 4篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 3篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1992年 | 1篇 |
1990年 | 1篇 |
1988年 | 1篇 |
排序方式: 共有194条查询结果,搜索用时 15 毫秒
151.
Hongmin Cao Mei Yang Yufeng Yang Jiayan Fang Yejia Cui 《Acta biochimica et biophysica Sinica》2021,(5):584-592
Oxaliplatin(OXA)resistance limits the efficiency of treatment for hepatocellular carcinoma(HCC).Studies have shown that the PDZ-binding kinase(PBK)plays importa... 相似文献
152.
Lian Fang Rui Feng Weiye Liang FangFang Liu Ganlan Bian Caiyong Yu Hongmin Guo Yihui Cao Mingkai Liu Jia Zuo Yinglong Peng Jie Zhao RuiXia Sun Jiajie Shan Jian Wang 《Journal of cellular and molecular medicine》2022,26(10):2908
Spermatogenesis is a cyclical process in which different generations of spermatids undergo a series of developmental steps at a fixed time and finally produce spermatids. Here, we report that overexpression of PD‐L1 (B7 homolog1) in the testis causes sperm developmental disorders and infertility in male mice, with severe malformation and sloughing during spermatid development, characterized by disorganized and collapsed seminiferous epithelium structure. PD‐L1 needs to be simultaneously expressed on Sertoli cells and spermatogonia to cause spermatogenesis failure. After that, we excluded the influence of factors such as the PD‐L1 receptor and humoral regulation, confirming that PD‐L1 has an intrinsic function to interact with PD‐L1. Studies have shown that PD‐L1 not only serves as a ligand but also plays a receptor‐like role in signal transduction. PD‐L1 interacts with PD‐L1 to affect the adhesive function of germ cells, causing malformation and spermatid sloughing. Taken together, these results indicate that PD‐L1 can interact with PD‐L1 to cause germ cell detachment and male infertility. 相似文献
153.
目的观察低聚果糖联合锌制剂对小儿迁延性腹泻的治疗效果,并探讨其对肠道菌群结构的影响。方法回顾102例小儿迁延性腹泻的临床资料,均接受常规治疗,其中有48例接受锌制剂治疗,标记为A组;余54例接受低聚果糖联合锌制剂治疗,标记为B组。比较排便次数、大便性状、饮食/母乳喂养恢复正常的时间,治疗效果,治疗前后肠道菌群结构及药物安全性。结果 B组排便次数恢复正常、大便性状恢复正常、饮食/母乳喂养恢复正常时间均短于A组(均P0.05);两组疗效等级差异具有统计学意义(P0.05),B组总有效率明显高于A组(P0.01);治疗后两组肠道微生态Chao1指数、Shannon指数均较治疗前升高(均P0.05),治疗后B组肠道微生态Chao1指数、Shannon指数均高于A组(均P0.05);2组治疗后双歧杆菌属、乳杆菌属、肠杆菌属水平相对丰度均增加,且B组均高于A组,2组治疗后梭菌属、漫游球菌属、乳球菌属、链球菌属、拟杆菌属、希瓦菌属、冷杆菌属、葡萄球菌属水平相对丰度均下降,且B组均低于A组,差异均有统计学意义(均P0.05);两组不良反应发生率接近(P0.05)。结论对小儿迁延性腹泻予以低聚果糖联合锌制剂可促进症状消失,增强疗效,还可调节肠道菌群结构,安全可靠。 相似文献
154.
Refolding of a fully functional flavivirus methyltransferase revealed that S‐adenosyl methionine but not S‐adenosyl homocysteine is copurified with flavivirus methyltransferase
下载免费PDF全文
![点击此处可从《Protein science : a publication of the Protein Society》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Matthew B. Brecher Zhong Li Jing Zhang Hui Chen Qishan Lin Binbin Liu Hongmin Li 《Protein science : a publication of the Protein Society》2015,24(1):117-128
Methylation of flavivirus RNA is vital for its stability and translation in the infected host cell. This methylation is mediated by the flavivirus methyltransferase (MTase), which methylates the N7 and 2′‐O positions of the viral RNA cap by using S‐adenosyl‐l ‐methionine (SAM) as a methyl donor. In this report, we demonstrate that SAM, in contrast to the reaction by‐product S‐adenosyl‐l ‐homocysteine, which was assumed previously, is copurified with the Dengue (DNV) and West Nile virus MTases produced in Escherichia coli (E. coli). This endogenous SAM can be removed by denaturation and refolding of the MTase protein. The refolded MTase of DNV serotype 3 (DNV3) displays methylation activity comparable to native enzyme, and its crystal structure at 2.1 Å is almost identical to that of native MTase. We characterized the binding of Sinefungin (SIN), a previously described SAM‐analog inhibitor of MTase function, to the native and refolded DNV3 MTase by isothermal titration calorimetry, and found that SIN binds to refolded MTase with more than 16 times the affinity of SIN binding to the MTase purified natively. Moreover, we show that SAM is also copurified with other flavivirus MTases, indicating that purification by refolding may be a generally applicable tool for studying flavivirus MTase inhibition. 相似文献
155.
156.
Behal RH Miller MS Qin H Lucker BF Jones A Cole DG 《The Journal of biological chemistry》2012,287(15):11689-11703
Chlamydomonas reinhardtii intraflagellar transport (IFT) particles can be biochemically resolved into two smaller assemblies, complexes A and B, that contain up to six and 15 protein subunits, respectively. We provide here the proteomic and immunological analyses that verify the identity of all six Chlamydomonas A proteins. Using sucrose density gradient centrifugation and antibody pulldowns, we show that all six A subunits are associated in a 16 S complex in both the cell bodies and flagella. A significant fraction of the cell body IFT43, however, exhibits a much slower sedimentation of ~2 S and is not associated with the IFT A complex. To identify interactions between the six A proteins, we combined exhaustive yeast-based two-hybrid analysis, heterologous recombinant protein expression in Escherichia coli, and analysis of the newly identified complex A mutants, ift121 and ift122. We show that IFT121 and IFT43 interact directly and provide evidence for additional interactions between IFT121 and IFT139, IFT121 and IFT122, IFT140 and IFT122, and IFT140 and IFT144. The mutant analysis further allows us to propose that a subset of complex A proteins, IFT144/140/122, can form a stable 12 S subcomplex that we refer to as the IFT A core. Based on these results, we propose a model for the spatial arrangement of the six IFT A components. 相似文献
157.
本研究拟通过小分子化合物氯化钴(CoCl2)模拟的低氧环境,探讨雷帕霉素(RPM)对该低氧下人急性髓细胞白血病HL-60细胞的生物学行为的影响。低氧模拟组、低氧雷帕霉素处理组、常氧雷帕霉素处理组HL-60细胞分别采用CoCl2、CoCl2/RPM、RPM进行处理,对照组为常氧下常规培养的HL-60细胞,处理及培养24h、48h、72h后收集细胞,采用倒置相差显微镜观察细胞生长状况,常规瑞氏染色后光学显微镜下观察细胞形态;MTT比色法检测各组细胞的活性和增殖能力;AnnexinV—FITC/PI双染法流式细胞术检测细胞凋亡。结果表明,与对照组细胞形态规则,胞核呈圆形或椭圆形相比,低氧模拟组和低氧雷帕霉素处理组细胞密度降低,生长明显受抑,细胞胞核呈不规则形或杆状,染色质粗糙,伴扭曲折叠等变化。各组间不同时问细胞增殖抑制率差异显著(P〈0.05),低氧模拟组和低氧雷帕霉素处理组增殖抑制率随着处理时间延长而增大,且低氧雷帕霉素处理组的增殖抑制率大于低氧模拟组。与常氧下的对照组及雷帕霉素处理组比较,低氧的模拟组和雷帕霉素处理组诱导细胞发生较明显的凋亡,且后期72h低氧雷帕霉素处理组凋亡率显著高于模拟低氧处理组。以上结果表明,模拟低氧环境下,HL-60细胞生长明显受抑制,且诱导细胞凋亡;雷帕霉素可增强对低氧对细胞的生长抑制和诱导凋亡作用。 相似文献
158.
Heikkinen A Tu H Pihlajaniemi T 《The international journal of biochemistry & cell biology》2012,44(5):714-717
Collagen XIII and the homologous collagens XXIII and XXV form a subgroup of type II transmembrane proteins within the collagen superfamily. Collagen XIII consists of a short cytosolic domain, a transmembrane domain and a large extracellular ectodomain, which may be shed into the pericellular matrix. It has been proposed that collagen XIII may function as an adhesion molecule, due to its cellular localization at focal contacts, numerous interactions with basement membrane (BM) and other extracellular matrix (ECM) proteins and expression at various cell-cell and cell-matrix junctions. Recent in vivo studies highlight its involvement in the development, differentiation and maturation of musculoskeletal tissues and vessels and in maintaining tissue integrity. 相似文献
159.
Sanam Sane Ammara Abdullah Morgan E. Nelson Hongmin Wang Subhash C. Chauhan Samuel S. Newton Khosrow Rezvani 《Cell stress & chaperones》2016,21(2):313-326
Overexpression of the oncoprotein mortalin in cancer cells and its protein partners enables mortalin to promote multiple oncogenic signaling pathways and effectively antagonize chemotherapy-induced cell death. A UBX-domain-containing protein, UBXN2A, acts as a potential mortalin inhibitor. This current study determines whether UBXN2A effectively binds to and occupies mortalin’s binding pocket, resulting in a direct improvement in the tumor’s sensitivity to chemotherapy. Molecular modeling of human mortalin’s binding pocket and its binding to the SEP domain of UBXN2A followed by yeast two-hybrid and His-tag pull-down assays revealed that three amino acids (PRO442, ILE558, and LYS555) within the substrate-binding domain of mortalin are crucial for UBXN2A binding to mortalin. As revealed by chase experiments in the presence of cycloheximide, overexpression of UBXN2A seems to interfere with the mortalin-CHIP E3 ubiquitin ligase and consequently suppresses the C‐terminus of the HSC70‐interacting protein (CHIP)-mediated destabilization of p53, resulting in its stabilization in the cytoplasm and upregulation in the nucleus. Overexpression of UBXN2A causes a significant inhibition of cell proliferation and the migration of colon cancer cells. We silenced UBXN2A in the human osteosarcoma U2OS cell line, an enriched mortalin cancer cell, followed by a clinical dosage of the chemotherapeutic agent 5-fluorouracil (5-FU). The UBXN2A knockout U2OS cells revealed that UBXNA is essential for the cytotoxic effect achieved by 5-FU. UBXN2A overexpression markedly increased the apoptotic response of U2OS cells to the 5-FU. In addition, silencing of UBXN2A protein suppresses apoptosis enhanced by UBXN2A overexpression in U2OS. The knowledge gained from this study provides insights into the mechanistic role of UBXN2A as a potent mortalin inhibitor and as a potential chemotherapy sensitizer for clinical application. 相似文献
160.
Ballabh P Xu H Hu F Braun A Smith K Rivera A Lou N Ungvari Z Goldman SA Csiszar A Nedergaard M 《Nature medicine》2007,13(4):477-485
The germinal matrix of premature infants is selectively vulnerable to hemorrhage within the first 48 h of life. To assess the role of vascular immaturity in germinal matrix hemorrhage (GMH), we evaluated germinal matrix angiogenesis in human fetuses and premature infants, as well as in premature rabbit pups, and noted active vessel remodeling in all three. Vascular endothelial growth factor (VEGF), angiopoietin-2 and endothelial cell proliferation were present at consistently higher levels in the germinal matrix relative to the white matter anlagen and cortical mantle. On that basis, we asked whether prenatal treatment with either of two angiogenic inhibitors, the COX-2 inhibitor celecoxib, or the VEGFR2 inhibitor ZD6474, could suppress the incidence of GMH in premature rabbit pups. Celecoxib treatment decreased angiopoietin-2 and VEGF levels as well as germinal matrix endothelial proliferation. Furthermore, treatment with celecoxib or ZD6474 substantially decreased the incidence of GMH. Thus, by suppressing germinal matrix angiogenesis, prenatal celecoxib or ZD6474 treatment may be able to reduce both the incidence and severity of GMH in susceptible premature infants. 相似文献