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排序方式: 共有69条查询结果,搜索用时 15 毫秒
21.
22.
Gregorio Oxilia Eugenio Bortolini Giulia Marciani Jessica Cristina Menghi Sartorio Antonino Vazzana Matteo Bettuzzi Daniele Panetta Simona Arrighi Federica Badino Carla Figus Federico Lugli Matteo Romandini Sara Silvestrini Rita Sorrentino Adriana Moroni Carlo Donadio Maria Pia Morigi Viviane Slon Marcello Piperno Sahra Talamo Carmine Collina Stefano Benazzi 《American journal of physical anthropology》2022,179(1):18-30
23.
Glantschnig H Hampton RA Lu P Zhao JZ Vitelli S Huang L Haytko P Cusick T Ireland C Jarantow SW Ernst R Wei N Nantermet P Scott KR Fisher JE Talamo F Orsatti L Reszka AA Sandhu P Kimmel D Flores O Strohl W An Z Wang F 《The Journal of biological chemistry》2010,285(51):40135-40147
Wnt/LRP5 signaling is a central regulatory component of bone formative and resorptive activities, and the pathway inhibitor DKK1 is a suppressor of bone formation and bone mass accrual in mice. In addition, augmented DKK1 levels are associated with high bone turnover in diverse low bone mass states in rodent models and disease etiologies in human. However, examination of the precise role of DKK1 in the normal skeleton and in higher species requires the development of refined DKK1-specific pharmacological tools. Here, we report the strategy resulting in isolation of a panel of fully human anti-DKK1 antibodies applicable to studies interrogating the roles of mouse, rhesus, and human DKK1. Selected anti-DKK1 antibodies bind primate and human DKK-1 with picomolar affinities yet do not appreciably bind to DKK2 or DKK4. Epitopes mapped within the DKK1 C-terminal domain necessary for interaction with LRP5/6 and consequently effectively neutralized DKK1 function in vitro. When introduced into naïve normal growing female mice, IgGs significantly improved trabecular bone volume and structure and increased both trabecular and cortical bone mineral densities in a dose-related fashion. Furthermore, fully human DKK1-IgG displayed favorable pharmacokinetic parameters in non-human primates. In summary, we demonstrate here a rate-limiting function of physiologic DKK1 levels in the regulation of bone mass in intact female mice, amendable to specific pharmacologic neutralization by newly identified DKK1-IgGs. Importantly the fully human IgGs display a profile of attributes that recommends their testing in higher species and their use in evaluating DKK1 function in relevant disease models. 相似文献
24.
A new assay for fatty acid desaturation 总被引:2,自引:0,他引:2
25.
André Strauss Rodrigo Elias Oliveira Danilo V. Bernardo Domingo C. Salazar-García Sahra Talamo Klervia Jaouen Mark Hubbe Sue Black Caroline Wilkinson Michael Phillip Richards Astolfo G. M. Araujo Renato Kipnis Walter Alves Neves 《PloS one》2015,10(9)
We present here evidence for an early Holocene case of decapitation in the New World (Burial 26), found in the rock shelter of Lapa do Santo in 2007. Lapa do Santo is an archaeological site located in the Lagoa Santa karst in east-central Brazil with evidence of human occupation dating as far back as 11.7–12.7 cal kyBP (95.4% interval). An ultra-filtered AMS age determination on a fragment of the sphenoid provided an age range of 9.1–9.4 cal kyBP (95.4% interval) for Burial 26. The interment was composed of an articulated cranium, mandible and first six cervical vertebrae. Cut marks with a v-shaped profile were observed in the mandible and sixth cervical vertebra. The right hand was amputated and laid over the left side of the face with distal phalanges pointing to the chin and the left hand was amputated and laid over the right side of the face with distal phalanges pointing to the forehead. Strontium analysis comparing Burial 26’s isotopic signature to other specimens from Lapa do Santo suggests this was a local member of the group. Therefore, we suggest a ritualized decapitation instead of trophy-taking, testifying for the sophistication of mortuary rituals among hunter-gatherers in the Americas during the early Archaic period. In the apparent absence of wealth goods or elaborated architecture, Lapa do Santo’s inhabitants seemed to use the human body to express their cosmological principles regarding death. 相似文献
26.
Effects of muscarinic, alpha-adrenergic, and substance P agonists and ionomycin on ion transport mechanisms in the rat parotid acinar cell. The dependence of ion transport on intracellular calcium 总被引:2,自引:1,他引:1 下载免费PDF全文
S P Soltoff M K McMillian L C Cantley E J Cragoe B R Talamo 《The Journal of general physiology》1989,93(2):285-319
The relationship between receptor-mediated increases in the intracellular free calcium concentration [( Ca]i) and the stimulation of ion fluxes involved in fluid secretion was examined in the rat parotid acinar cell. Agonist-induced increases in [Ca]i caused the rapid net loss of up to 50-60% of the total content of intracellular chloride (Cli) and potassium (Ki), which is consistent with the activation of calcium-sensitive chloride and potassium channels. These ion movements were accompanied by a 25% reduction in the intracellular volume. The relative magnitudes of the losses of Ki and the net potassium fluxes promoted by carbachol (a muscarinic agonist), phenylephrine (an alpha-adrenergic agonist), and substance P were very similar to their characteristic effects on elevating [Ca]i. Carbachol stimulated the loss of Ki through multiple efflux pathways, including the large-conductance Ca-activated K channel. Carbachol and substance P increased the levels of intracellular sodium (Nai) to more than 2.5 times the normal level by stimulating the net uptake of sodium through multiple pathways; Na-K-2Cl cotransport accounted for greater than 50% of the influx, and approximately 20% was via Na-H exchange, which led to a net alkalinization of the cells. Ionomycin stimulated similar fluxes through these two pathways, but also promoted sodium influx through an additional pathway which was nearly equivalent in magnitude to the combined uptake through the other two pathways. The carbachol-induced increase in Nai and decrease in Ki stimulated the activity of the sodium pump, measured by the ouabain-sensitive rate of oxygen consumption, to nearly maximal levels. In the absence of extracellular calcium or in cells loaded with the calcium chelator BAPTA (bis[o-aminophenoxy]ethane-N,N,N',N'-tetraacetic acid) the magnitudes of agonist- or ionomycin-stimulated ion fluxes were greatly reduced. The parotid cells displayed a marked desensitization to substance P; within 10 min the elevation of [Ca]i and alterations in Ki, Nai, and cell volume spontaneously returned to near baseline levels. In addition to quantitating the activation of various ion flux pathways in the rat parotid acinar cell, these results demonstrate that the activation of ion transport systems responsible for fluid secretion in this tissue is closely linked to the elevation of [Ca]i. 相似文献
27.
Richard C. Talamo 《Life sciences》1975,16(5):811-812
28.
Action and metabolism of bradykinin in dog lung 总被引:1,自引:0,他引:1
29.
Philippe Neuner Andrea M. Peier Fabio Talamo Paolo Ingallinella Armin Lahm Gaetano Barbato Annalise Di Marco Kunal Desai Karolina Zytko Ying Qian Xiaobing Du Davide Ricci Edith Monteagudo Ralph Laufer Alessandro Pocai Elisabetta Bianchi Donald J. Marsh Antonello Pessi 《Journal of peptide science》2014,20(1):7-19
Neuromedin U (NMU) is an endogenous peptide implicated in the regulation of feeding, energy homeostasis, and glycemic control, which is being considered for the therapy of obesity and diabetes. A key liability of NMU as a therapeutic is its very short half‐life in vivo. We show here that conjugation of NMU to human serum albumin (HSA) yields a compound with long circulatory half‐life, which maintains full potency at both the peripheral and central NMU receptors. Initial attempts to conjugate NMU via the prevalent strategy of reacting a maleimide derivative of the peptide with the free thiol of Cys34 of HSA met with limited success, because the resulting conjugate was unstable in vivo. Use of a haloacetyl derivative of the peptide led instead to the formation of a metabolically stable conjugate. HSA–NMU displayed long‐lasting, potent anorectic, and glucose‐normalizing activity. When compared side by side with a previously described PEG conjugate, HSA–NMU proved superior on a molar basis. Collectively, our results reinforce the notion that NMU‐based therapeutics are promising candidates for the treatment of obesity and diabetes. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
30.
Benjamin Stich Bettina IG Haussmann Raj Pasam Sankalp Bhosale C Tom Hash Albrecht E Melchinger Heiko K Parzies 《BMC plant biology》2010,10(1):216