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441.
Human Y-79 Retinoblastoma Cells Exhibit Specific Corticotropin-Releasing Hormone Binding Sites 总被引:2,自引:1,他引:1
Abstract: In this study we have identified specific binding sites for corticotropin-releasing hormone (CRH) in human Y-79 retinoblastoma cell membranes by using 125 I-Tyrovine CRH (125 I-oCRH) as radioligand. Binding at 19°C was rapid with steady state being reached within 20 min, reversible and linear with membrane protein concentration. The 125 I-oCRH binding was enhanced by Mg2+ and inhibited by the GTP analogue guanosine 5'- O -(3'-thiotriphosphate). Y-79 cell membranes exhibited two populations of binding sites, a high-affinity site with an apparent dissociation constant ( K D ) of 1 n M and a low-affinity site with an apparent K D of 500 n M . 125 I-oCRH binding was completely antagonized by human/rat CRH, [Met(O)21 ]oCRH, α-helical CRH9–41 , urotensin I, and sauvagine with a rank order of potency similar to that displayed by CRH receptors of other tissues. These data describe for the first time the presence of specific CRH-binding sites in retinal cells. The Y-79 cell line may therefore constitute a valuable model in which to study CRH action on retinal cells. 相似文献
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Lucia Gregorio-Teruel Pierluigi Valente Beiying Liu Gregorio Fernández-Ballester Feng Qin Antonio Ferrer-Montiel 《Biophysical journal》2015,109(3):529-541
Transient receptor potential vanilloid subtype I (TRPV1) is a thermosensory ion channel that is also gated by chemical substances such as vanilloids. Adjacent to the channel gate, this polymodal thermoTRP channel displays a TRP domain, referred to as AD1, that plays a role in subunit association and channel gating. Previous studies have shown that swapping the AD1 in TRPV1 with the cognate from the TRPV2 channel (AD2) reduces protein expression and produces a nonfunctional chimeric channel (TRPV1-AD2). Here, we used a stepwise, sequential, cumulative site-directed mutagenesis approach, based on rebuilding the AD1 domain in the TRPV1-AD2 chimera, to unveil the minimum number of amino acids needed to restore protein expression and polymodal channel activity. Unexpectedly, we found that virtually full restitution of the AD1 sequence is required to reinstate channel expression and responses to capsaicin, temperature, and voltage. This strategy identified E692, R701, and T704 in the TRP domain as important for TRPV1 activity. Even conservative mutagenesis at these sites (E692D/R701K/T704S) impaired channel expression and abolished TRPV1 activity. However, the sole mutation of these positions in the TRPV1-AD2 chimera (D692E/K701R/S704T) was not sufficient to rescue channel gating, implying that other residues in the TRP domain are necessary to endow activity to TRPV1-AD2. A biophysical analysis of a functional chimera suggested that mutations in the TRP domain raised the energetics of channel gating by altering the coupling of stimuli sensing and pore opening. These findings indicate that inter- and/or intrasubunit interactions in the TRP domain are essential for correct TRPV1 gating. 相似文献
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Calcium transients in single fibers of low-frequency stimulated fast-twitch muscle of rat 总被引:4,自引:0,他引:4
Carroll Stefanie; Nicotera Pierluigi; Pette Dirk 《American journal of physiology. Cell physiology》1999,277(6):C1122
Ca2+transients were investigated in single fibers isolated from ratextensor digitorum longus muscles exposed to chronic low-frequency stimulation for different time periods up to 10 days. Approximately 2.5-fold increases in resting Ca2+ concentration([Ca2+]) were observed 2 h after stimulationonset and persisted throughout the stimulation period. The elevated[Ca2+] levels were in the range characteristicof slow-twitch fibers from soleus muscle. In addition, we noticed atransitory elevation of the integral[Ca2+] per pulse with a maximum (~5-fold)after 1 day. Steep decreases in rate constant of[Ca2+] decay could be explained by an immediateimpairment of Ca2+ uptake and, with longer stimulationperiods, by an additional loss of cytosolic Ca2+ bindingcapacity resulting from a decay in parvalbumin content. A partialrecovery of the rate constant of [Ca2+] decayin 10-day stimulated muscle could be explained by an increasing mitochondrial contribution to Ca2+ sequestration. 相似文献
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Michael Rost Tenzin Wangmo Felix Niggli Karin Hartmann Heinz Hengartner Marc Ansari Pierluigi Brazzola Johannes Rischewski Maja Beck-Popovic Thomas Kühne Bernice S. Elger 《Journal of bioethical inquiry》2017,14(4):555-565
The goal is to present how shared decision-making in paediatric oncology occurs from the viewpoints of parents and physicians. Eight Swiss Pediatric Oncology Group centres participated in this prospective study. The sample comprised a parent and physician of the minor patient (<18 years). Surveys were statistically analysed by comparing physicians’ and parents’ perspectives and by evaluating factors associated with children’s actual involvement. Perspectives of ninety-one parents and twenty physicians were obtained for 151 children. Results indicate that for six aspects of information provision examined, parents’ and physicians’ perceptions differed. Moreover, parents felt that the children were more competent to understand diagnosis and prognosis, assessed the disease of the children as worse, and reported higher satisfaction with decision-making on the part of the children. A patient’s age and gender predicted involvement. Older children and girls were more likely to be involved. In the decision-making process, parents held a less active role than they actually wanted. Physicians should take measures to ensure that provided information is understood correctly. Furthermore, they should work towards creating awareness for systematic differences between parents and physicians with respect to the perception of the child, the disease, and shared decision-making. 相似文献
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Rita Meleddu Serenella Deplano Elias Maccioni Francesco Ortuso Filippo Cottiglia Daniela Secci Alessia Onali Erica Sanna Andrea Angeli Rossella Angius Stefano Alcaro Claudiu T. Supuran Simona Distinto 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):685
A small library of coumarin and their psoralen analogues EMAC10157a-b-d-g and EMAC10160a-b-d-g has been designed and synthesised to investigate the effect of structural modifications on their inhibition ability and selectivity profile towards carbonic anhydrase isoforms I, II, IX, and XII. None of the new compounds exhibited activity towards hCA I and II isozymes. Conversely, both coumarin and psoralen derivatives were active against tumour associated isoforms IX and XII in the low micromolar or nanomolar range of concentration. These data further corroborate our previous findings on analogous derivatives, confirming that both coumarins and psoralens are interesting scaffolds for the design of isozyme selective hCA inhibitors. 相似文献