全文获取类型
收费全文 | 5449篇 |
免费 | 412篇 |
国内免费 | 583篇 |
专业分类
6444篇 |
出版年
2024年 | 9篇 |
2023年 | 75篇 |
2022年 | 181篇 |
2021年 | 318篇 |
2020年 | 217篇 |
2019年 | 243篇 |
2018年 | 259篇 |
2017年 | 187篇 |
2016年 | 241篇 |
2015年 | 329篇 |
2014年 | 416篇 |
2013年 | 411篇 |
2012年 | 520篇 |
2011年 | 456篇 |
2010年 | 297篇 |
2009年 | 289篇 |
2008年 | 314篇 |
2007年 | 270篇 |
2006年 | 214篇 |
2005年 | 153篇 |
2004年 | 168篇 |
2003年 | 142篇 |
2002年 | 96篇 |
2001年 | 78篇 |
2000年 | 84篇 |
1999年 | 74篇 |
1998年 | 45篇 |
1997年 | 48篇 |
1996年 | 46篇 |
1995年 | 40篇 |
1994年 | 29篇 |
1993年 | 27篇 |
1992年 | 26篇 |
1991年 | 17篇 |
1990年 | 17篇 |
1989年 | 19篇 |
1988年 | 9篇 |
1987年 | 9篇 |
1986年 | 9篇 |
1985年 | 10篇 |
1984年 | 6篇 |
1983年 | 3篇 |
1979年 | 8篇 |
1975年 | 7篇 |
1974年 | 4篇 |
1971年 | 4篇 |
1970年 | 4篇 |
1969年 | 2篇 |
1966年 | 3篇 |
1965年 | 3篇 |
排序方式: 共有6444条查询结果,搜索用时 15 毫秒
121.
122.
123.
新城疫病毒FMW株体外溶瘤作用及其机制分析 总被引:1,自引:0,他引:1
[目的]筛选出能高效抑制多种人肿瘤细胞生长增殖的新城疫(New Castle disease virus,NDV)毒株,为进一步构建重组高效靶向溶瘤毒株奠定基础.[方法]以体外噻唑蓝法测定NDV对A549、SMMC7721等肿瘤细胞及人胚干细胞L-02、人胚肾细胞HEK293等的生长抑制率,空斑试验确定病毒滴度及感染复数.利用形态学观察、Hoechst荧光染色、流式细胞术及免疫印迹等分析了NDV-FMW诱导肿瘤细胞凋亡的细胞生物学变化及其机制.[结果]从近50株NDV中筛选出NDV-FMW,以20 MOI病毒作用A549、SMMC7721等肿瘤细胞48 h,细胞生长抑制率达60%,NDV-FMW诱导肿瘤细胞发生凋亡,效应呈时间和剂量的依赖性,凋亡细胞出现核染色质断裂、浓缩及二倍体亚峰,细胞周期阻滞于GO/G1期,此外,病毒感染A549细胞16 h后开始检测到活化的Caspase-3裂解片段及PARP裂解大片段.[结论]NDV-FMW株体外能高效抑制肿瘤细胞的增殖,并经Caspase-3途径诱导肿瘤细胞凋亡.FMW株具有自主知识产权,其良好的体外溶瘤能力为进一步探讨体内抗肿瘤及临床试验的进行奠定了基础,并有可能为恶性肿瘤的治疗提供新的生物制剂. 相似文献
124.
禽致病性大肠杆菌安徽分离株luxS和pfs基因的克隆、表达与细胞外合成AI-2 活性检测 总被引:1,自引:0,他引:1
【目的】LuxS/AI-2型密度感应系统存在于革兰氏阴性和阳性菌中,可产生用于细菌种间交流的通用自诱导信号分子AI-2(Autoinducer-2,AI-2),细菌许多生理功能都受此系统的调节。本研究开展对禽致病性大肠杆菌(Avian Pathogenic Escherichia coli,APEC)自诱导信号分子AI-2的检测和建立体外合成、定量的方法,为进一步研究APEC的AI-2调控作用奠定基础。【方法】利用哈维弧菌BB170(Vibrio harveyi BB170)开展对APEC AI-2的检测;利用表达、纯化的LuxS和Pfs在体外催化S-腺苷同型半胱氨酸(Sadenosylhomocysteine,SAH),进行AI-2的体外合成。【结果】APEC能产生自诱导信号分子AI-2;成功表达可用于AI-2合成的可溶性重组蛋白LuxS和Pfs;纯化的重组蛋白LuxS和Pfs与SAH同时作用后,合成了浓度为300μmol/L的AI-2;运用哈维弧菌BB170对合成的AI-2活性检测表明,其活性是阴性对照的700倍。【结论】APEC存在LuxS/AI-2型密度感应系统,APEC的LuxS和Pfs可以在体外催化SAH生成有活性的AI-2分子。本研究为进一步研究APEC的AI-2的调控作用奠定基础。 相似文献
125.
益生菌通过调整正常菌群缓解酒精性肝损伤的研究进展 总被引:1,自引:0,他引:1
许多临床试验表明慢性酒精性肝损伤会引起肠道菌群的失调,主要表现为双歧杆菌、乳杆菌数量减少,革兰氏阴性菌大量繁殖,破坏肠道屏障功能,增加肠道通透性,使细菌来源的内毒素大量释放出来,引起血液内毒素增加,并在肝脏中累积,超出肝脏的清除能力,导致肝损伤。本文主要综述益生菌通过调整正常菌群这一机制来缓解酒精性肝损伤的研究进展,进而深入了解酒精引起肠道菌群变化(酒精的摄入会导致肠道中拟杆菌、厚壁菌数量减少,革兰氏阴性变形菌、革兰氏阳性放线菌数量增加,同时肠道内细菌来源的内毒素水平增加)导致肝损伤的发病机制,以及益生菌如何通过调整肠道正常菌群改善酒精性肝损伤。 相似文献
126.
Xiaowei Wei Wei Ma Hui Gu Dan Liu Wenting Luo Songying Cao Shanshan Jia Tianchu Huang Yiwen He Yuzuo Bai Weilin Wang Zhengwei Yuan 《Cell proliferation》2023,56(2)
ObjectivesSpina bifida aperta (SBA) is one of the most common neural tube defects. Neural injury in SBA occurs in two stages involving failed neural tube closure and progressive degeneration through contact with the amniotic fluid. We previously suggested that intra‐amniotic bone marrow‐derived mesenchymal stem cell (BMSC) therapy for fetal rat SBA could achieve beneficial functional recovery through lesion‐specific differentiation. The aim of this study is to examine whether the amniotic fluid microenvironment can be improved by intra‐amniotic BMSC transplantation.MethodsThe intra‐amniotic BMSC injection was performed using in vivo rat fetal SBA models. The various cytokine expressions in rat amniotic fluid were screened by protein microassays. Intervention experiments were used to study the function of differentially expressed cytokines.ResultsA total of 32 cytokines showed significant upregulated expression in the BMSC‐injected amniotic fluid. We focused on Activin A, NGF, BDNF, CNTF, and CXCR4. Intervention experiments showed that the upregulated Activin A, NGF, BDNF, and CNTF could inhibit apoptosis and promote synaptic development in fetal spinal cords. Inhibiting the activity of these factors weakened the anti‐apoptotic and pro‐differentiation effects of transplanted BMSCs. Inhibition of CXCR4 activity reduced the engraftment rate of BMSCs in SBA fetuses.ConclusionBMSC transplantation can improve the amniotic fluid environment, and this is beneficial for SBA repair.In utero intra‐amniotic BMSC or PBS microinjection in the E15 fetuses was performed in E15 rat fetuses with spina bifida aperta, and amniotic fluid was collected at E21 for protein array detection. Venn diagram shows the relationship of three biological processes (GO: 0030335, 0048699, and 0043524) and the attribution of differentially expressed proteins. Comparative analysis of five proteins with the largest fold changes in the process of generation of neurons. 相似文献
127.
Atractylenolide I (Atr-I) was found to sensitize a variety of human cancer cells in previous studies. Purinergic P2X7R plays important role in different cancers. However, whether Atr-I could generate antitumor activity in human cervical cancer cells and P2X7R get involved in this effect remain unclear. In this study, Hela (HPV 18 +) and SiHa (HPV 16 +) cells were treated with different doses of Atr-I. The results indicated that agonist and antagonist of P2X7 receptors, BzATP and JNJ-47965567 (JNJ), could suppress the proliferation of Hela and SiHa cells. Atr-I demonstrated a considerable antitumor effect in both human cervical cancer cells in vitro. Atr-I combined with P2X7R agonist, BzATP, restored Atr-I-induced growth inhibition in Hela cells but not in SiHa cells. However, the combinatorial treatment of P2X7R antagonist JNJ and Atr-I has an additive effect on cell growth inhibition in SiHa cells rather than in Hela cells. It implied that P2X7R would get involved in the anti-human cervical cancer cells effect of Atr-I. 相似文献
128.
Bo Qin Qian Bai Dan Yan Fanxiang Yin Zhu Zhu Chaoyuan Xia Yang Yang Yi Zhao 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):1995
A series of 1,2,3-triazole analogues as novel fat mass and obesity-associated protein (FTO) inhibitors were synthesised in this study. Among all 1,2,3-triazoles, compound C6 exhibited the most robust inhibition of FTO with an IC50 value of 780 nM. It displayed the potent antiproliferative activity against KYSE-150, KYSE-270, TE-1, KYSE-510, and EC109 cell lines with IC50 value of 2.17, 1.35, 0.95, 4.15, and 0.83 μM, respectively. In addition, C6 arrested the cell cycle at G2 phase against TE-1 and EC109 cells in a concentration-dependent manner. Analysis of cellular mechanisms demonstrated that C6 concentration-dependently regulated epithelial mesenchymal transition (EMT) pathway and PI3K/AKT pathway against TE-1 and EC109 cells. Molecular docking studies that C6 formed important hydrogen-bond interaction with Lys107, Asn110, Tyr108, and Leu109 of FTO. These findings suggested that C6 as a novel FTO inhibitor and orally antitumor agent deserves further investigation to treat esophageal cancer. 相似文献
129.
130.