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261.
Isakovic A Harhaji L Stevanovic D Markovic Z Sumarac-Dumanovic M Starcevic V Micic D Trajkovic V 《Cellular and molecular life sciences : CMLS》2007,64(10):1290-1302
The present study reports for the first time a dual antiglioma effect of the well-known antidiabetic drug metformin. In low-density
cultures of the C6 rat glioma cell line, metformin blocked the cell cycle progression in G0/G1 phase without inducing significant cell death. In confluent C6 cultures, on the other hand, metformin caused massive induction
of caspase-dependent apoptosis associated with c-Jun N-terminal kinase (JNK) activation, mitochondrial depolarization and
oxidative stress. Metformin-triggered apoptosis was completely prevented by agents that block mitochondrial permeability transition
(cyclosporin A) and oxygen radical production (N-acetylcisteine), while the inhibitors of JNK activation (SP600125) or glycolysis
(sodium fluoride, iodoacetate) provided partial protection. The antiglioma effect of metformin was reduced by compound C,
an inhibitor of AMP-activated protein kinase (AMPK), and was mimicked by the AMPK agonist AICAR. Similar effects were observed
in the human glioma cell line U251, while rat primary astrocytes were completely resistant to the antiproliferative and proapoptotic
action of metformin.
Received 14 February 2007; received after revision 26 March 2007; accepted 3 April 2007 相似文献
262.
Tauopathies are a group of neurodegenerative diseases characterised by intracellular deposits of the microtubule-associated
protein tau. The most typical example of a tauopathy is Alzheimer’s disease. The importance of tau in neuronal dysfunction
and degeneration has been demonstrated by the discovery of dominant mutations in the MAPT gene, encoding tau, in some rare dementias. Recent developments have shed light on the significance of tau phosphorylation
and aggregation in pathogenesis. Furthermore, emerging evidence reveals the central role played by tau pre-mRNA processing
in tauopathies. The present review focuses on the current understanding of tau-dependent pathogenic mechanisms and how realistic
therapies for tauopathies can be developed.
Received 3 December 2006; received after revision 23 February 2007; accepted 20 March 2007 相似文献
263.
Decoding the Hedgehog signal in animal development 总被引:4,自引:0,他引:4
The Hedgehog (Hh) family of secreted proteins plays essential roles in a myriad of developmental processes via a complex signaling
cascade conserved in species ranging from insects to mammals. In many developmental contexts, Hh acts as long-range morphogen
to control distinct cellular outcomes as a function of its concentration. Here we review the current understanding of the
Hh signaling mechanisms that govern the establishment of the Hh gradient and the transduction of the Hh signal with an emphasis
on the intracellular signaling cascade from the receptor to the nuclear effector. We discuss how graded Hh signals are transduced
to govern distinct developmental outcomes.
Received 28 October 2005; received after revision 6 February 2006; accepted 15 February 2006 相似文献
264.
265.
266.
Fabre AC Vantourout P Champagne E Tercé F Rolland C Perret B Collet X Barbaras R Martinez LO 《Cellular and molecular life sciences : CMLS》2006,63(23):2829-2837
We have previously demonstrated on human hepatocytes that apolipoprotein A-I binding to an ecto-F1-ATPase stimulates the production of extracellular ADP that activates a P2Y13-mediated high-density lipoprotein (HDL) endocytosis pathway. Therefore, we investigated the mechanisms controlling the extracellular
ATP/ADP level in hepatic cell lines and primary cultures to determine their impact on HDL endocytosis. Here we show that addition
of ADP to the cell culture medium induced extracellular ATP production that was due to adenylate kinase
and nucleoside diphosphokinase
activities, but not to ATP synthase activity. We further observed that in vitro modulation of both ecto-NDPK and AK activities could regulate the ADP-dependent HDL endocytosis. But interestingly, only
AK appeared to naturally participate in the pathway by consuming the ADP generated by the ecto-F1-ATPase. Thus controlling the extracellular ADP level is a potential target for reverse cholesterol transport regulation.
Received 13 July 2006; received after revision 29 August 2006; accepted 19 September 2006 相似文献
267.
268.
本实验旨在研究野生型与stn7突变体在光合性能上的差异.实验包括检测种子萌发状况、用脉冲幅度调制成像荧光计IMAG-MINI测量叶绿素含量、用SPAD-502叶绿素仪测量SPAD值以及用LI-6400XT便携式光合仪测量叶绿素荧光动力学参数并用photosynthesis软件拟合光响应曲线及相关参数.结果显示,WT和stn7植株的种子萌发情况和SPAD值几乎无差异,叶绿素荧光动力学参数显示WT的光合性能比stn7植株高,叶绿素a/b和光响应曲线的结果得出WT利用弱光的能力较强,光响应曲线结果还显示高光强下,stn7植株光合速率较高.本文研究发现STN7激酶在调节水稻的光合作用中发挥着重要作用. 相似文献
269.
目的研究发现,细胞周期素依赖性激酶(cyclin dependent kinases,CDKs)家族成员与食管鳞癌的发病密切相关,但细胞周期素依赖性激酶16(CDK16)对食管鳞癌发病的影响尚不清楚.本研究旨在探讨CDK16在人食管鳞癌组织中的表达及生物学意义.方法应用组织芯片技术结合免疫组织化学技术检测45例食管鳞癌组织、45例癌旁组织中CDK16蛋白的表达情况,并使用统计分析软件研究CDK16蛋白的表达与食管鳞癌临床病理特征之间的关系.结果 CDK16在食管鳞癌组织中呈阳性表达,且表达强度与肿瘤分化程度呈负相关.另外,CDK16在食管鳞癌细胞中的表达位置与肿瘤的分化程度紧密相关.CDK16的表达与食管鳞癌的分化程度、淋巴结转移及TNM临床分期均具有显著的相关性(P<0.05),而与患者的年龄、性别以及肿瘤的部位、最大径、病理形态没有显著的相关性(P>0.05).结论 CDK16在食管鳞癌中的高表达与食管鳞癌的发生发展及转移密切相关.检测CDK16的表达有助于食管鳞癌的临床诊断和预后评估. 相似文献
270.
通过克隆形成能力实验以及体内移植实验,发现当敲除小鼠MLL-AF9细胞中的受体结合蛋白1(RIP1)基因后,相对于WT MLL-AF9细胞,其克隆形成能力明显减弱,移植后小鼠生存时间延长了3倍以上.在组织切片观察中,WT MLL-AF9细胞移植小鼠出现明显白血病发病特征,而RIP1~(-/-)MLL-AF9细胞移植小鼠的切片显示正常.当将RIP1中的激酶活性位点突变后,相对于WT MLL-AF9细胞,在移植实验中小鼠生存时间明显延长.对病发小鼠的脾脏细胞流式分析结果表明:激酶活性位点突变后致病能力明显减弱,提示RIP1基因的缺失会导致MLL-AF9致病能力减弱. 相似文献