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L. Selmeci E. Pósch Julia Mosonyi L. Hársing 《Cellular and molecular life sciences : CMLS》1981,37(1):24-25
Summary Unilateral ureteral obstruction in rats, resulted in considerable alterations of polyamine levels in the obstructed kidney during a 72-h observation period, as compared with respective values for the contralateral control kidney.This work was supported in part by the Ministry of Health, Hungary (1-04-0301-03-02/H). The skilful technical assistance of Ms G. Mayer and Mrs I. Harmos is highly appreciated. 相似文献
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Knabl J Witschi R Hösl K Reinold H Zeilhofer UB Ahmadi S Brockhaus J Sergejeva M Hess A Brune K Fritschy JM Rudolph U Möhler H Zeilhofer HU 《Nature》2008,451(7176):330-334
Inflammatory diseases and neuropathic insults are frequently accompanied by severe and debilitating pain, which can become chronic and often unresponsive to conventional analgesic treatment. A loss of synaptic inhibition in the spinal dorsal horn is considered to contribute significantly to this pain pathology. Facilitation of spinal gamma-aminobutyric acid (GABA)ergic neurotransmission through modulation of GABA(A) receptors should be able to compensate for this loss. With the use of GABA(A)-receptor point-mutated knock-in mice in which specific GABA(A) receptor subtypes have been selectively rendered insensitive to benzodiazepine-site ligands, we show here that pronounced analgesia can be achieved by specifically targeting spinal GABA(A) receptors containing the alpha2 and/or alpha3 subunits. We show that their selective activation by the non-sedative ('alpha1-sparing') benzodiazepine-site ligand L-838,417 (ref. 13) is highly effective against inflammatory and neuropathic pain yet devoid of unwanted sedation, motor impairment and tolerance development. L-838,417 not only diminished the nociceptive input to the brain but also reduced the activity of brain areas related to the associative-emotional components of pain, as shown by functional magnetic resonance imaging in rats. These results provide a rational basis for the development of subtype-selective GABAergic drugs for the treatment of chronic pain, which is often refractory to classical analgesics. 相似文献
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John Davenport Julia Davenport Cheong-Hoong Diong K.H. Low 《Journal of Natural History》2016,50(33-34):2097-2105
The pig-nosed freshwater turtle Carettochelys insculpta Ramsay, 1886 has paddle-shaped foreflippers that resemble those of sea turtles. These turtles exhibit a wide range of swimming capabilities. As well as swimming by the action of synchronized foreflippers alone, they sometimes used alternate hindlimb action at the same time. They could swim by ipsilaterally synchronized action of all four limbs, or by hindlimb action alone (combined with stabilizer/lift function of the foreflippers). The turtles also showed flexibility in bottom-walking. Besides the ipsilaterally synchronized quadrupedal action characteristic of other freshwater turtles, they exhibited a bipedal walking mechanism never previously described. Propelled by alternate action of the hindlimbs, the animals held the head and plastron above the substratum, with the large foreflippers acting to provide anterior lift and stability against roll and yaw. Because both hindlimbs were sometimes off the substratum simultaneously during bipedal locomotion, their duty factors were < 0.5, implying a bipedal run. 相似文献
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Vivek S. Peche Tad A. Holak Bhagyashri D. Burgute Kosmas Kosmas Sushant P. Kale F. Thomas Wunderlich Fatiha Elhamine Robert Stehle Gabriele Pfitzer Klaus Nohroudi Klaus Addicks Florian Stöckigt Jan W. Schrickel Julia Gallinger Michael Schleicher Angelika A. Noegel 《Cellular and molecular life sciences : CMLS》2013,70(3):527-543
Cyclase-associated proteins are highly conserved proteins that have a role in the regulation of actin dynamics. Higher eukaryotes have two isoforms, CAP1 and CAP2. To study the in vivo function of CAP2, we generated mice in which the CAP2 gene was inactivated by a gene-trap approach. Mutant mice showed a decrease in body weight and had a decreased survival rate. Further, they developed a severe cardiac defect marked by dilated cardiomyopathy (DCM) associated with drastic reduction in basal heart rate and prolongations in atrial and ventricular conduction times. Moreover, CAP2-deficient myofibrils exhibited reduced cooperativity of calcium-regulated force development. At the microscopic level, we observed disarrayed sarcomeres with development of fibrosis. We analyzed CAP2’s role in actin assembly and found that it sequesters G-actin and efficiently fragments filaments. This activity resides completely in its WASP homology domain. Thus CAP2 is an essential component of the myocardial sarcomere and is essential for physiological functioning of the cardiac system, and a deficiency leads to DCM and various cardiac defects. 相似文献
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PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
Day CL Kaufmann DE Kiepiela P Brown JA Moodley ES Reddy S Mackey EW Miller JD Leslie AJ DePierres C Mncube Z Duraiswamy J Zhu B Eichbaum Q Altfeld M Wherry EJ Coovadia HM Goulder PJ Klenerman P Ahmed R Freeman GJ Walker BD 《Nature》2006,443(7109):350-354
Functional impairment of T cells is characteristic of many chronic mouse and human viral infections. The inhibitory receptor programmed death 1 (PD-1; also known as PDCD1), a negative regulator of activated T cells, is markedly upregulated on the surface of exhausted virus-specific CD8 T cells in mice. Blockade of this pathway using antibodies against the PD ligand 1 (PD-L1, also known as CD274) restores CD8 T-cell function and reduces viral load. To investigate the role of PD-1 in a chronic human viral infection, we examined PD-1 expression on human immunodeficiency virus (HIV)-specific CD8 T cells in 71 clade-C-infected people who were naive to anti-HIV treatments, using ten major histocompatibility complex (MHC) class I tetramers specific for frequently targeted epitopes. Here we report that PD-1 is significantly upregulated on these cells, and expression correlates with impaired HIV-specific CD8 T-cell function as well as predictors of disease progression: positively with plasma viral load and inversely with CD4 T-cell count. PD-1 expression on CD4 T cells likewise showed a positive correlation with viral load and an inverse correlation with CD4 T-cell count, and blockade of the pathway augmented HIV-specific CD4 and CD8 T-cell function. These data indicate that the immunoregulatory PD-1/PD-L1 pathway is operative during a persistent viral infection in humans, and define a reversible defect in HIV-specific T-cell function. Moreover, this pathway of reversible T-cell impairment provides a potential target for enhancing the function of exhausted T cells in chronic HIV infection. 相似文献
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