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排序方式: 共有267条查询结果,搜索用时 46 毫秒
111.
In the present study we describe heterodimerization, trafficking, coupling to adenylyl cyclase and signaling in HEK-293 cells cotransfected with human-somatostatin receptor 5 (hSSTR5) and β1-adrenergic receptor (β1AR). hSSTR5/β1AR exists as heterodimers in basal conditions which was further enhanced upon synergistic activation of both receptors. Activation of either β1AR or hSSTR5 displayed dissociation of heterodimerization. In cotransfectants, β1AR effect on cAMP was predominant; however, blocking β1AR with antagonist resulted in 60% inhibition of forskolin-stimulated cAMP in the presence of hSSTR5 agonists. cAMP/PKA pathway in cotransfected cells was regulated in receptor-specific manner, in contrast, the status of pERK1/2 and pPI3K/AKT was predominantly regulated by hSSTR5. The expression levels of phosphorylated NFAT remained unchanged indicating blockade of calcineurin-mediated dephosphorylation and nuclear translocation of NFAT, the process predominantly regulated by pJNK in SSTR5 dependent manner. Taken together, the functional consequences of results described here might have relevance in the cardiovascular system where SSTR and AR subtypes play important roles. 相似文献
112.
Processing of somatostatin precursors: evidence for enzymatic cleavage by hypothalamic extract 总被引:2,自引:0,他引:2
The action of enzymes extracted from rat hypothalamus on the previously characterized high molecular weight forms of hypothalamic somatostatin-like immunoreactivity (4 K SLI and 25 K SLI) has been investigated in vitro in order to further define the role of these molecules as possible precursors for tetradecapeptide somatostatin (SRIF). Studies of the degradation of endogenous SLI and of synthetic SRIF by hypothalamic enzymes showed that the time course of breakdown of endogenous SLI is markedly slower than that of synthetic SRIF due to the relative stability of 25 K SLI as well as the generation of at least two new immunoreactive molecules. Incubation of purified 25 K SLI with SLI-free hypothalamic extract showed after 10 to 30 min newly formed immunoreactive material of an intermediate size between 25 K SLI and 4 K SLI and after 60 min the emergence of material coeluting with SRIF. These data show that the hypothalamus contains the enzymes necessary for degrading endogenous SLI and for processing the 25 K SLI molecule to SRIF providing further evidence that 25 K SLI might be a biosynthetic precursor for SRIF. 相似文献
113.
《Neuron》2020,105(3):522-533.e4
114.
115.
Han L Liang AX Zhang J Fang M Hua GH Sang L Geng LY Wang HR Yang LG 《Animal : an international journal of animal bioscience》2008,2(11):1569-1574
Somatostatin (SS) is a hormone that inhibits the secretion of growth hormone. Immunization against SS can promote the growth of animals. A novel SS-VP22 fused vaccine, pEGS2SS-V, was constructed from pEGS2SS plasmid with a VP22 gene fragment. Two times of immunization with pEGS2SS-V-induced anti-SS antibodies in mice. Compared with mice immunized with pEGS2SS and 0.85% saline, the growth performance of mice immunized with pEGS2SS-V was increased by 14.1% (P < 0.05) and 48.4% (P < 0.01) on the 2nd week after the first vaccination, respectively. The results indicated that the effects of the somatostatin DNA vaccine could be improved effectively by VP22 gene adjuvant. 相似文献
116.
Interactions Among Gastric Somatostatin, Interleukin-8 and Mucosal Inflammation in Helicobacter pylori-Positive Peptic Ulcer Patients 总被引:4,自引:0,他引:4
Sayuri Yamamoto Hiroshi Kaneko Toshihiro Konagaya Shozaburo Mori Hiroshi Kotera Toshihiko Hayakawa Chikara Yamaguchi Motoaki Uruma Kazuo Kusugami Terunori Mitsuma 《Helicobacter》2001,6(2):136-145
Background. To investigate whether Helicobacter pylori infection, but not drugs, affects gastric somatostatin, interleukin‐8 (IL‐8), histological inflammation through eradication therapy, and interactions among these parameters. Methods. Twenty‐eight H. pylori‐positive patients (21 males; mean age 47.0 years) with either gastric ulcer (GU: n = 11) or duodenal ulcer (n = 17) diagnosed endoscopically were treated with dual therapy. Eradication was defined as negative microbiologic tests and 13C‐urea breath test. Levels of antral and gastric juice somatostatin and mucosal IL‐8 were measured by radioimmunoassay and enzyme‐linked immunosorbent assay, respectively. Histology was assessed by the Sydney system. Results. H. pylori was eradicated in 15 patients (10 males, 6 GU) out of 28 (54%). The patients’ backgrounds did not affect the eradication of H. pylori. Successes in eradication significantly increased antral and juice somatostatin contents, and dramatically decreased IL‐8 levels and histological gastritis. In contrast, persistent H. pylori infection did not affect somatostatin and histological gastritis. An inverse correlation was present between changes in somatostatin levels and histological activity. No relationship was observed in changed values between antral somatostatin and IL‐8. Conclusions. These results indicate that eradication of H. pylori, but not the drugs used, induced an increase in somatostatin levels in the antrum and gastric juice, suggesting a close relationship between H. pylori and gastric somatostatin regulation. A close correlation between an increase in gastric somatostatin levels and the normalization of histological activity was present, suggesting that certain peptide‐immune interactions in the gastric mucosa exist in H. pylori infection. 相似文献
117.
The purpose of this research was to study the chemical reactivity of a somatostatin analogue octreotide acetate, formulated
in microspheres with polymers of varying molecular weight and co-monomer ratio under in vitro testing conditions. Poly(D,L-lactide-co-glycolide)
(PLGA) and poly(D,L-lactide) (PLA) microspheres were prepared by a solvent extraction/evaporation method. The microspheres
were characterized for drug load, impurity content, and particle size. Further, the microspheres were subjected to in vitro
release testing in acetate buffer (pH 4.0) and phosphate buffered saline (PBS) (pH 7.2). In acetate buffer, 3 microsphere
batches composed of low molecular weight PLGA 50∶50, PLGA 85∶15, and PLA polymers (≤10 kDa) showed 100% release with minimal
impurity formation (<10%). The high molecular weight PLGA 50∶50 microspheres (28 kDa) displayed only 70% cumulative release
in acetate buffer with significant impurity formation (∼24%). In PBS (pH 7.4), on the other hand, only 50% release was observed
with the same low molecular weight batches (PLGA 50∶50, PLGA 85∶15, and PLA) with higher percentages of hydrophobic impurity
formation (ie, 40%, 26%, and 10%, respectively). In addition, in PBS, the high molecular weight PLGA 50∶50 microspheres showed
only 20% drug release with ∼60% mean impurity content. The chemically modified peptide impurities inside microspheres were
structurally confirmed through Fourier transform-mass spectrometry (FT-MS) and liquid chromatography/mass spectrometry (LC-MS/MS)
analyses after extraction procedures. The adduct compounds were identified as covalently modified conjugates of octreotide
with lactic and glycolic acid monomers within polymeric microspheres. The data suggest that due to steric hindrance factors,
polymers with greater lactide content were less amenable to the formation of adduct impurities compared with PLGA 50∶50 copolymers. 相似文献
118.
《Médecine Nucléaire》2019,43(4):316-322
Despite the existence of biological markers of aggressiveness, the clinical course of gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NEN) remains difficult to predict. Discrepancies between imaging data generated with 111In-pentetreotide scintigraphy and 18F-FDG-PET could reflect the degree of cellular de-differentiation. NEN patients with both types of studies were identified retrospectively from the SwissNET database, which is collecting information on Swiss NEN patients since 2008. Progression free survival (PFS) and overall survival (OS) were assessed depending on functional imaging results. Correlation between histological grading (according to the WHO 2010 classification) and functional imaging status was also assessed. We identified 31 patients with both imaging studies, either on the primary tumor site (21/31) or for metastases (21/31), with 12/31 on both sites. Mean follow-up was 36 months (95% CI 27–45). 21 patients had a metastatic disease at diagnosis and 11 died at follow-up. 7/31 (22%) were NET G1, 16/31 (52%) were NET G2 and 8/31 (26%) were NEC G3. Only 18F-FDG PET status almost reached statistical significance (P = 0.054) with histological grading. Progression free-survival was significantly poorer in the 18F-FDG positive group (n = 21), with a median time for progression of 8 months, compared to 51 months in the negative group (n = 10) with a HR of 3.2 (97.5% CI 1.1–9.5, P = 0.04). Overall survival tended to be worse with a positive PET and a negative 111In-pentetreotide scintigraphy status with a HR 1.63 (97.5%CI 0.11–21, P = 0.08). 111In-pentetreotide scintigraphy status was not found to be predictive of survival nor progression.ConclusionThese data demonstrate the poorer prognostic value of a positive 18F-FDG-PET imaging in this cohort of patients. 相似文献
119.
Rainbow trout gill tissue was used to examine the role of somatostatin (SS) on insulin-like growth factor-I (IGF-I) receptor expression. In vivo implantation of fish with somatostatin-14 (SS-14) reduced expression of IGF-I receptor mRNAs as well as [(125)I]-IGF-I binding. In vitro incubation of gill filaments with SS-14 or various SS isoforms, including SS-28 and [Tyr(7), Gly(10)]-SS-14-containing peptides, directly inhibited IGF-I receptor mRNA expression. SS-14 also inhibited [(125)I]-IGF-I binding in vitro. These data indicate that SSs inhibit the mRNA and functional expression of IGF-I receptors in gill, and suggest that SSs regulate growth in an extrapituitary manner by reducing sensitivity to IGF-I. 相似文献
120.
Lauren L. Radford Dionysia Papagiannopoulou Fabio Gallazzi Ashley Berendzen Lisa Watkinson Terry Carmack Michael R. Lewis Silvia S. Jurisson Heather M. Hennkens 《Bioorganic & medicinal chemistry》2019,27(3):492-501
The somatostatin receptor subtype 2 (SSTR2) is often highly expressed on neuroendocrine tumors (NETs), making it a popular in vivo target for diagnostic and therapeutic approaches aimed toward management of NETs. In this work, an antagonist peptide (sst2-ANT) with high affinity for SSTR2 was modified at the N-terminus with a novel [N,S,O] bifunctional chelator (2) designed for tridentate chelation of rhenium(I) and technetium(I) tricarbonyl cores, [Re(CO)3]+ and [99mTc][Tc(CO)3]+. The chelator-peptide conjugation was performed via a Cu(I)-assisted click reaction of the alkyne-bearing chelator (2) with an azide-functionalized sst2-ANT peptide (3), to yield NSO-sst2-ANT (4). Two synthetic methods were used to prepare Re-4 at the macroscopic scale, which differed based on the relative timing of the click conjugation to the [Re(CO)3]+ complexation by 2. The resulting products demonstrated the expected molecular mass and nanomolar in vitro SSTR2 affinity (IC50 values under 30?nM, AR42J cells, [125I]iodo-Tyr11-somatostatin-14 radioligand standard). However, a difference in their HPLC retention times suggested a difference in metal coordination modes, which was attributed to a competing N-triazole donor ligand formed during click conjugation. Surprisingly, the radiotracer scale reaction of [99mTc][Tc(OH2)3(CO)3]+ (99mTc; t½?=?6?h, 141?keV γ) with 4 formed a third product, distinct from the Re analogues, making this one of the unusual cases in which Re and Tc chemistries are not well matched. Nevertheless, the [99mTc]Tc-4 product demonstrated excellent in vitro stability to challenges by cysteine and histidine (≥98% intact through 24?h), along with 75% stability in mouse serum through 4?h. In vivo biodistribution and microSPECT/CT imaging studies performed in AR42J tumor-bearing mice revealed improved clearance of this radiotracer in comparison to a similar [99mTc][Tc(CO)3]-labeled sst2-ANT derivative previously studied. Yet despite having adequate tumor uptake at 1?h (4.9% ID/g), tumor uptake was not blocked by co-administration of a receptor-saturating dose of SS-14. Aimed toward realignment of the Re and Tc product structures, future efforts should include distancing the alkyne group from the intended donor atoms of the chelator, to reduce the coordination options available to the [M(CO)3]+ core (M?=?Re, 99mTc) by disfavoring involvement of the N-triazole. 相似文献