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201.
Preferred conformation of endomorphin-1 in aqueous and membrane-mimetic environments. 总被引:2,自引:0,他引:2
The newly discovered endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) are potent opioid peptides with the highest affinity and selectivity for the mu receptor among all known endogenous ligands. To investigate a possible correlation between these biological properties and the conformational preferences of the small peptides, a comparative structural analysis was performed of endomorphin-1 in aqueous buffer and in membrane-mimicking SDS and AOT normal and reverse micelles by the use of CD, FT-IR, fluorescence and(1)H-NMR spectroscopy. It is well established for opioid peptides that, independently of the receptor selectivity, the Tyr1 residue plays the role of the primary pharmacophore and that the orientation of the second aromatic pharmacophore relative to the tyrosine side-chain dictates the mu or delta-receptor selectivity. By varying the environment of endomorphin-1 from water to the amphipathic SDS micelles and even more efficiently to the AOT reverse micelles, the display of the aromatic side-chains changes from an interaction of the Tyr1 and Phe4 residues to a switch of the Trp3 indole group into close contact with the phenolic moiety to prevent this type of interaction and to force an orientation of the Phe4 side-chain into the opposite direction. This conformational switch is accompanied by a stabilization of the cis -Pro2 isomer and the resulting spatial array of the pharmacophoric groups correlate well with the structural model of mu receptor-bound opioid peptides. The results indicate that AOT reverse micelles with a woof 10, where almost exclusively ordered water is secluded in the cavity, constitute with their electrostatic and hydrophobic potential an excellent mimetic of amphipathic surfaces as present on lipid bilayers and on ligand-recognition and ligand-binding sites of proteins. 相似文献
202.
Roato I D'Amelio P Gorassini E Grimaldi A Bonello L Fiori C Delsedime L Tizzani A De Libero A Isaia G Ferracini R 《PloS one》2008,3(11):e3627
Background
Bone forming metastases are a common and disabling consequence of prostate cancer (CaP). The potential role of osteoclast activity in CaP bone metastases is not completely explained. In this study, we investigated ex vivo whether the osteolytic activity is present and how it is ruled in CaP patients with bone forming metastases.Methodology
Forty-six patients affected by newly diagnosed CaP and healthy controls were enrolled. At diagnosis, 37 patients had a primary tumour only, while 9 had primary tumour and concomitant bone forming metastases. In all patients there was no evidence of metastasis to other non-bone sites. For all patients and controls we collected blood and urinary samples. We evaluated patients'' bone homeostasis; we made peripheral blood mononuclear cell (PBMC) cultures to detect in vitro osteoclastogenesis; we dosed serum expression of molecules involved in cancer induced osteoclatogenesis, such as RANKL, OPG, TNF-alpha, DKK-1 and IL-7. By Real-Time PCR, we quantified DKK-1 and IL-7 gene expression on micro-dissected tumour and healthy tissue sections.Principal Findings
CaP bone metastatic patients showed bone metabolism disruption with increased bone resorption and formation compared to non-bone metastatic patients and healthy controls. The CaP PBMC cultures showed an enhanced osteoclastogenesis in bone metastatic patients, due to an increase of RANKL/OPG ratio. We detected increased DKK-1 serum levels and tissue gene expression in patients compared to controls. IL-7 resulted high in patients'' sera, but its tissue gene expression was comparable in patients and controls.Conclusions
We demonstrated ex vivo that osteoclastogenesis is an active mechanism in tumour nesting of bone forming metastatic cancer and that serum DKK-1 levels are increased in CaP patients, suggesting to deeply investigate its role as tumour marker. 相似文献203.
Petroleum exploration and extraction are common on the Patagonian steppe, but their impacts on the native biodiversity have not been properly evaluated. We describe both activities in a Patagonian nature reserve and consider their potential impacts on biodiversity. More than 2025 km of seismic lines inside the reserve resulted in 87.21 m2/ha (0.9%) of directly affected land, and 793 fragments of native habitats were defined with a mean area of 1.26 ± 0.74 km2. Vegetation recovery on seismic lines is extremely poor. We discuss the role of seismic lines as barriers to native species, and their significance in encouraging poaching and the expansion of exotic invasive plants. There is a high degree of overlap between current petroleum activities and areas of special conservation concern (high erosion risk, vegetation diversity, abundance of endemic plant species, and habitat quality for native vertebrates). All these have a significant impact on the efficiency of the conservation area and highlight the urgent need to implement appropriate mitigating actions. 相似文献
204.
Patrizia Cardelli Anna Fiori † Vito D. Corleto Maria Rosaria Savi † Filippo Granata ‡ Fabrizio Ceci Giampiero Ferraguti Rosa Luisa Potenza † Gianfranco Delle Fave § Robert T. Jensen¶ Roberto Strom 《Journal of neurochemistry》2001,78(2):349-357
In the presence of somatostatin-14 or some of its receptorial agonists, the uptake of large neutral amino acids by isolated brain microvessels was found to be inhibited up to 50%, no other transport system being affected. Although the luminal and abluminal sides of brain endothelial cells are both capable of taking up large neutral amino acids, only uptake from the abluminal side appears to be inhibited by somatostatin. The involvement of a type-2 somatostatin receptor was suggested by assays with a series of receptor-specific somatostatin agonists, and was confirmed by the release of inhibition caused by a specific type-2 receptor antagonist. A type-2-specific mRNA was indeed shown to be present in both bovine brain microvessels ex vivo and primary cultures of endothelial cells from rat brain microvessels. 相似文献
205.
206.
207.
The 67-kDa laminin receptor originated from a ribosomal protein that acquired a dual function during evolution 总被引:8,自引:0,他引:8
Ardini E; Pesole G; Tagliabue E; Magnifico A; Castronovo V; Sobel ME; Colnaghi MI; Menard S 《Molecular biology and evolution》1998,15(8):1017-1025
The 67-kDa laminin receptor (67LR) is a nonintegrin cell surface receptor
that mediates high-affinity interactions between cells and laminin.
Overexpression of this protein in tumor cells has been related to tumor
invasion and metastasis. Thus far, only a full-length gene encoding a
37-kDa precursor protein (37LRP) has been isolated. The finding that the
cDNA for the 37LRP is virtually identical to a cDNA encoding the ribosomal
protein p40 has suggested that 37LRP is actually a component of the
translational machinery, with no laminin-binding activity. On the other
hand, a peptide of 20 amino acids deduced from the sequence of 37LR/p40 was
shown to exhibit high laminin-binding activity. The evolutionary
relationship between 23 sequences of 37LRP/p40 proteins was analyzed. This
phylogenetic analysis indicated that all of the protein sequences derive
from orthologous genes and that the 37LRP is indeed a ribosomal protein
that acquired the novel function of laminin receptor during evolution. The
evolutionary analysis of the sequence identified as the laminin-binding
site in the human protein suggested that the acquisition of the
laminin-binding capability is linked to the palindromic sequence LMWWML,
which appeared during evolution concomitantly with laminin.
相似文献
208.
1. Antlions are opportunistic trap building predators that cannot control prey encounter. Their trap should ideally retain a great diversity of prey. However, building a single trap that captures many prey with varying characteristics can be challenging. 2. A series of five different ant species ranging from thin to large, of sizes ranging from 2.75 to 6.5 mm, and a mean weight ranging from 0.54 to 6.00 mg were offered in a random succession to antlions. The state of satiation of the antlions was controlled, and their mass and the depth of their pit were recorded. The reaction of antlion to the prey, the probability of capture as well as the time to escape were recorded. 3. The probability of an antlion reaction is an increasing function of the pit depth and a decreasing function of antlion mass. The probability of capture is highest for intermediate prey mass and is an increasing function of pit depth. The time to escape is a declining function of prey mass and an increasing function of pit depth. 4. There is an upper limit to prey mass given that large prey escape out of the pit. There is a lower limit to prey mass given the difficulty to apprehend the smallest, thin species. Consequently, there is a range of prey mass, corresponding to a medium‐sized ant of 2 mg, for which the pit functions best. The physics of insect locomotion on sandy slopes was identified as the key to understanding the functioning of antlion pits. 相似文献
209.
Inhibition of High-Affinity Choline Uptake and Acetylcholine Synthesis by Quinuclidinyl and Hemicholinium Derivatives 总被引:1,自引:1,他引:0
Gerald H. Sterling Peter H. Doukas†‡ Fiori J. Ricciardi Jr. ‡ Diane W. Biedrzycka John J. O'Neill† 《Journal of neurochemistry》1986,46(4):1170-1175
Choline uptake into cholinergic neurons for acetylcholine (ACh) synthesis is by a specific, high-affinity, sodium- and temperature-dependent transport mechanism (HAChU). To assess the role of choline availability in regulation of ACh synthesis, the structure-activity relationships of several hemicholinium (HC) and quinuclidinyl analogs were evaluated in a dose response manner. As confirms previous studies, the HCs, e.g., HC-3, acetylsecohemicholinium, and HC-15 are potent inhibitors of HAChU, HC-3 being the most potent (I50 = 6.1 X 10(-8) M). In the present study, the most potent quinuclidinyl derivative was the N-methyl-3-quinuclidinone (I50 = 5.6 X 10(-7) M). This compound had approximately 100-fold greater inhibitory activity than the corresponding racemic alcohol, suggesting that the 3-hydroxyl functional group is not absolutely essential for activity. Increasing the size of the N-functional group from a methyl to an allyl in the alcohol led to a 10-fold increase in activity. However, removal of the quaternizing N-methyl group yielding the tertiary amine, 3-quinuclidinol hydrochloride, greatly reduced its capacity to inhibit HAChU. Of the 2-benzylidene-3-quinuclidinone derivatives studied, only the m-chloro derivative significantly reduced HAChU. 相似文献
210.
A Fiori P Benciolini 《Bollettino della Società italiana di biologia sperimentale》1969,45(23):1483-1486