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51.
ddy小鼠替代大鼠的经济简便的抗焦虑药筛选改进模型--间氯苯哌嗪诱导的小鼠明暗箱焦虑模型 总被引:2,自引:0,他引:2
目的建立一个部分模拟临床病理的简便易得、经济有效的用于筛选和研制抗焦虑药的模型.方法用间氯苯哌嗪(mCPP)诱导产生焦虑,观察ddy小鼠和ICR小鼠在明暗箱的行为表现.结果 mCPP在SC 1-4mg/kg的剂量下即可显著降低ddy小鼠在明箱的活动次数,而对暗箱的活动次数影响不显著;1mg/kg与4mg/kg组比较,在明箱的活动次数无显著差异;mCPP在SC 2-10mg/kg的剂量下对ICR小鼠在明箱的的活动次数影响不太显著,只在10mg/kg剂量下才显著;而对暗箱的活动次数却影响较大,在2mg/kg的剂量下即可显著降低活动次数.用安定对该模型进行验证,发现只用较小的样本量即可得出显著结果.结论用ddy小鼠可以取代Wistar大鼠建立mCPP诱导焦虑的明暗箱模型,在样本量较小的情况下即可得到有效结果.所以是一个能够克服大鼠实验缺点的、简便易得且经济有效的用于筛选和研制抗焦虑药的良好模型.但用mCPP诱导的焦虑模型对小鼠的种属有选择性,ICR小鼠不适于上述模型. 相似文献
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53.
Yokoi N Komeda K Wang HY Yano H Kitada K Saitoh Y Seino Y Yasuda K Serikawa T Seino S 《Nature genetics》2002,31(4):391-394
The autoimmune disease type 1 diabetes mellitus (insulin-dependent diabetes mellitus, IDDM) has a multifactorial etiology. So far, the major histocompatibility complex (MHC) is the only major susceptibility locus that has been identified for this disease and its animal models. The Komeda diabetes-prone (KDP) rat is a spontaneous animal model of human type 1 diabetes in which the major susceptibility locus Iddm/kdp1 accounts, in combination with MHC, for most of the genetic predisposition to diabetes. Here we report the positional cloning of Iddm/kdp1 and identify a nonsense mutation in Cblb, a member of the Cbl/Sli family of ubiquitin-protein ligases. Lymphocytes of the KDP rat infiltrate into pancreatic islets and several tissues including thyroid gland and kidney, indicating autoimmunity. Similar findings in Cblb-deficient mice are caused by enhanced T-cell activation. Transgenic complementation with wildtype Cblb significantly suppresses development of the KDP phenotype. Thus, Cblb functions as a negative regulator of autoimmunity and Cblb is a major susceptibility gene for type 1 diabetes in the rat. Impairment of the Cblb signaling pathway may contribute to human autoimmune diseases, including type 1 diabetes. 相似文献
54.
T Aoyagi T Wada F Kojima M Nagai S Harada T Takeuchi K Isse M Ogura M Hamamoto K Tanaka 《Experientia》1992,48(7):656-659
Previously we reported that there is a kallikrein deficiency in the cerebral tissue of patients with Alzheimer-type dementia. The present study was performed to investigate protease changes in the serum of these patients. The results showed that the kallikrein activity was normal, but that the activities of plasmin and urokinase were significantly low. The present findings indicate a derangement in the clotting and fibrinolytic systems in Alzheimer patients. 相似文献
55.
Uemura M Kato T Ishioka R Yamaoka H Monard B Nogami D Maehara H Sugie A Takahashi S 《Nature》2003,423(6942):843-844
Gamma-ray bursts (GRBs) are energetic explosions that for 0.01-100 s are the brightest gamma-ray sources in the sky. Observations of the early evolution of afterglows are expected to provide clues about the nature of the bursts, but their rapid fading has hampered such studies; some recent rapid localizations of bursts have improved the situation. Here we report an early detection of the very bright afterglow of the burst of 29 March 2003 (GRB030329). Our data show that, even early in the afterglow phase, the light curve shows unexpectedly complicated structures superimposed on the fading background. 相似文献
56.
Crystal structure of the RNA-binding domain of the U1 small nuclear ribonucleoprotein A 总被引:100,自引:0,他引:100
The crystal structure of the RNA binding domain of the U1 small nuclear ribonucleoprotein A, which forms part of the ribonucleoprotein complex involved in the excision of introns, has been solved. It contains a four-stranded beta sheet and two alpha helices. The highly conserved segments designated RNP1 and RNP2 lie side by side on the middle two beta strands. U1 RNA binding studies of mutant proteins suggest that the RNA binds to the four-stranded beta sheet and to the flexible loops on one end. 相似文献
57.
58.
Distal residues in the oxygen binding site of haemoglobin studied by protein engineering 总被引:4,自引:0,他引:4
K Nagai B Luisi D Shih G Miyazaki K Imai C Poyart A De Young L Kwiatkowsky R W Noble S H Lin 《Nature》1987,329(6142):858-860
The geometries of the Fe-O2 and Fe-CO bonds in myoglobin and haemoglobin differ significantly from those in free porphyrin model compounds. It has been suggested that steric hindrance by Val-E11 and His-E7 and a hydrogen bond between His-E7 and oxygen affect the geometry and electronic state of the Fe-ligand bond, and that these interactions may be important in controlling oxygen affinity. We have produced mutant haemoglobins in E. coli having Val(67 beta)E11 replaced by Ala, Met, Leu or Ile and His(58 beta)E7 by Gln, Val or Gly. We have studied the effect of these mutations on the equilibrium and kinetics of ligand binding. The conformation of the new side chains and their effect on the protein structure have been examined by X-ray crystallography, and the vibrational properties of the Fe-CO bond observed by resonance Raman spectroscopy. We found that the steric hindrance of ligand binding by the E11 residue and the polarity of the E7 residue in the beta subunit are critical for fine-tuning ligand affinity. 相似文献
59.
探讨加用气流阻力负荷(FRL) 状态下流速容量(FV) 曲线检查对初检OSA 患者的意义对象为24 名健康成年男性及21 例男性阻塞性睡眠呼吸暂停(OSA) 患者经整夜多导睡眠仪检查诊断或排除OSA模拟实验结果发现只有同时加上可陷闭管及FRL 时,才出现显著吸气气流受限无FRL时,FV 曲线( 以FEF50/FIF50 比值大于1 为指标) 检查发现OSA的敏感性和特异性分别为33 .3 % 和91 .6 % ,阳性预测率为63 .6 % 加用FRL 时敏感性为76 .2 % ,特异性为75 % ,阳性预测率为72 .2 % 吸、呼气相峰值流速比值及中期峰值流速比值与OSA 严重呈显著相关联合应用加FRL及常规FL曲线检查可能对OSA 患者初筛有较高价值 相似文献
60.
Rock MJ Prenen J Funari VA Funari TL Merriman B Nelson SF Lachman RS Wilcox WR Reyno S Quadrelli R Vaglio A Owsianik G Janssens A Voets T Ikegawa S Nagai T Rimoin DL Nilius B Cohn DH 《Nature genetics》2008,40(8):999-1003
The brachyolmias constitute a clinically and genetically heterogeneous group of skeletal dysplasias characterized by a short trunk, scoliosis and mild short stature. Here, we identify a locus for an autosomal dominant form of brachyolmia on chromosome 12q24.1-12q24.2. Among the genes in the genetic interval, we selected TRPV4, which encodes a calcium permeable cation channel of the transient receptor potential (TRP) vanilloid family, as a candidate gene because of its cartilage-selective gene expression pattern. In two families with the phenotype, we identified point mutations in TRPV4 that encoded R616Q and V620I substitutions, respectively. Patch clamp studies of transfected HEK cells showed that both mutations resulted in a dramatic gain of function characterized by increased constitutive activity and elevated channel activation by either mechano-stimulation or agonist stimulation by arachidonic acid or the TRPV4-specific agonist 4alpha-phorbol 12,13-didecanoate (4alphaPDD). This study thus defines a previously unknown mechanism, activation of a calcium-permeable TRP ion channel, in skeletal dysplasia pathogenesis. 相似文献