全文获取类型
收费全文 | 361篇 |
免费 | 38篇 |
出版年
2021年 | 3篇 |
2018年 | 4篇 |
2016年 | 9篇 |
2015年 | 10篇 |
2014年 | 9篇 |
2013年 | 14篇 |
2012年 | 14篇 |
2011年 | 10篇 |
2010年 | 12篇 |
2009年 | 13篇 |
2008年 | 8篇 |
2007年 | 9篇 |
2006年 | 14篇 |
2005年 | 8篇 |
2004年 | 14篇 |
2003年 | 10篇 |
2002年 | 13篇 |
2001年 | 9篇 |
2000年 | 16篇 |
1999年 | 15篇 |
1998年 | 7篇 |
1997年 | 5篇 |
1996年 | 7篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 8篇 |
1990年 | 4篇 |
1989年 | 9篇 |
1988年 | 8篇 |
1987年 | 5篇 |
1986年 | 7篇 |
1985年 | 10篇 |
1984年 | 5篇 |
1983年 | 7篇 |
1981年 | 4篇 |
1980年 | 6篇 |
1979年 | 8篇 |
1978年 | 5篇 |
1977年 | 11篇 |
1976年 | 5篇 |
1975年 | 5篇 |
1974年 | 7篇 |
1973年 | 5篇 |
1972年 | 6篇 |
1971年 | 4篇 |
1969年 | 3篇 |
1968年 | 6篇 |
1967年 | 2篇 |
排序方式: 共有399条查询结果,搜索用时 31 毫秒
71.
Opiate stimulation of prolactin (PRL) release appears to involve a hypothalamic mechanism(s). The present study utilized both central acting drugs and direct measurement of hypothalamic dopamine (DA) to investigate this problem. Administration of L-dopa, the precursor of DA; piribedil, a DA agonist; or amineptine, a DA reuptake inhibitor, each decreased serum PRL concentrations. Morphine sulfate (MS) and haloperidol (HAL) significantly increased serum PRL levels. L-dopa and piribedil reversed the stimulatory effect of MS on serum PRL concentrations by increasing dopamine activity. MS blocked the inhibitory effects of amineptine on serum PRL release, possibly by decreasing the concentration of DA available for reuptake. Injection of subeffective doses of HAL concurrently with a subeffective dose of MS increased serum PRL concentrations, by an additive inhibitory action on dopaminergic activity. β-endorphin, an endogenous opioid peptide, decreased the rate of DA turnover in the median eminence, and increased serum PRL levels approximately 10 - fold. These observations indicate that opiates stimulate PRL release by decreasing DA activity in the median eminence. 相似文献
72.
M. Di Renzo A. L. Pasqui F. Bruni M. Saletti G. Bova C. Chiarion A. Carducci A. Auteri 《Luminescence》1997,12(4):193-197
Common variable immunodeficiency is a primary immunodeficiency characterized by a failure of antibody synthesis, whose fundamental immunologic abnormality is still unknown. In our study, we evaluated some immune functions using chemiluminescence in a 32-year-old woman affected by common variable immunodeficiency. In particular, we showed an impairment of her lymphomonocyte proliferative response which was evaluated using a method based on the bioluminescent measurement of ATP. Besides, we found a reducton of her lymphomonocyte IL2 and IL4 production: the IL4 production was evaluated through an ELISA method, whereas the IL2 activity was determined by its ability to support the IL2-dependent murine T-cell line (CTLL) proliferation which was established through a method based on the bioluminescent measurement of ATP. Finally, we evaluated both yeast-induced and fMLP-induced polymorphonuclear and monocyte oxidative metabolism through a luminol-amplified chemiluminescence; these functions were within normal values. Therefore, in our patient affected by common variable immunodeficiency, we demonstrated an impairment of cellular immunity, which might contribute to the pathogenesis of the disease. © 1997 John Wiley & Sons, Ltd. 相似文献
73.
74.
Guerrini G Ciciani G Cambi G Bruni F Selleri S Melani F Montali M Martini C Ghelardini C Norcini M Costanzo A 《Bioorganic & medicinal chemistry》2008,16(8):4471-4489
The synthesis and binding studies of a series of 3-acylpyrazolo[5,1-c][1,2,4]benzotriazine 5-oxides 8-substituted are reported. High-affinity ligands at benzodiazepine site on GABA(A) receptor complex (GABA(A)/BzR complex) were obtained when the 3-aroyl substituent is represented by a five-member heteroaroyl ring (furoyl-, thenoyl-, and pyrroyl-). Moreover the type of heteroaroyl ring at position 3 influences the feature of the substituent at position 8 to obtain high-affinity ligands: a 'hydrogen-bond acceptor ring' at position 3 is synergic with an electron donor substituent at position 8, while a 'hydrogen-bond donor ring' is synergic with a withdrawing substituent. Compounds 8a, 9b, and 11 were deeply studied in vivo for their pharmacological effects considering six potential benzodiazepine actions: motor coordination, anticonvulsant action, spontaneous motor activity and explorative activity, anxiolytic-like effects, mouse learning and memory modulation, and ethanol-potentiating action. To rationalize and qualitatively interpret the GABA(A)/Bz binding affinities of compounds 8a and 11, a dynamic molecular modeling study has been performed, with the aim of assessing the preferred geometry of protein-ligand complex. 相似文献
75.
Donati C Cencetti F De Palma C Rapizzi E Brunelli S Cossu G Clementi E Bruni P 《Cellular signalling》2009,21(2):228-236
Mesoangioblasts are vessel-derived progenitor cells that can be induced to differentiate into different cell types of the mesoderm such as muscle and bone. Here we examined the role of transforming growth factor-beta (TGFbeta), a pleiotropic cytokine that plays a major role in development and specifically induces smooth muscle differentiation of mesoangioblasts, in the regulation of death and survival of these cells. TGFbeta exerts a marked anti-apoptotic action in mesoangioblasts with a mechanism involving regulation of sphingosine kinase 1 (SphK1), one of the isoforms responsible for S1P formation. Treatment with the cytokine efficaciously protected mesoangioblasts from apoptosis induced by serum starvation or staurosporine treatment assessed by various means such as activation of caspase-3, determination of cytoplasmic histone-associated-DNA-fragments and PE-AnnexinV staining. The protective action of TGFbeta from staurosporine-induced apoptosis was strongly reduced when the SphK activity was inhibited by drugs, when SphK1 but not SphK2 was downregulated by specific siRNA and when a SphK1 dominant negative mutant was overexpressed. Staurosporine treatment induced down-regulation of both SphK isoforms and TGFbeta rescued SphK1 but not SphK2 expression. Interestingly, TGFbeta strongly enhanced SphK activity during staurosporine-induced cell death. Both TGFbeta-induced SphK1 up-regulation and TGFbeta anti-apoptotic action were found to be dependent on p42/44 MAPK activation. 相似文献
76.
Alessandro Piergentili Wilma Quaglia Fabio Del Bello Mario Giannella Maria Pigini Elisabetta Barocelli Simona Bertoni Rosanna Matucci Marta Nesi Bruno Bruni Massimo Di Vaira 《Bioorganic & medicinal chemistry》2009,17(24):8174-8185
Novel analogues of cis-N,N,N-trimethyl-(6-methyl-1,4-dioxan-2-yl)methanaminium iodide (2a) were synthesized by inserting methyl groups alternatively or simultaneously in positions 5 and 6 of the 1,4-dioxane nucleus in all combinations. Their biological profile was assessed by receptor binding assays at human muscarinic M1–M5 receptors stably expressed in CHO cells and by functional studies performed on classical isolated organ preparations, namely, rabbit electrically stimulated vas deferens, and guinea pig electrically stimulated left atrium, ileum, and lung strips. The results showed that the simultaneous presence of one methyl group in both positions 5 and 6 with a trans stereochemical relationship with each other (diastereomers 4 and 5) or the geminal dimethylation in position 6 (compound 8) favour the selective activation of M3 receptors. Compounds 4, 5, and 8 might be valuable tools in the characterization of the M3 receptor, as well as provide useful information for the design and development of novel selective M3 antagonists. 相似文献
77.
Guerrini G Costanzo A Ciciani G Bruni F Selleri S Costagli C Besnard F Costa B Martini C De Siena G Malmberg-Aiello P 《Bioorganic & medicinal chemistry》2006,14(3):758-775
The synthesis and the binding study of new 3-arylesters and 3-heteroarylpyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide 8-substituted are reported. The nature of these substituents (in terms of lipophilic and electronic features) seems to influence the binding affinity. High-affinity ligands were studied in mice in vivo for their pharmacological effects, considering six potential benzodiazepine actions: anxiolytic-like effects, muscle relaxant effects, motor coordination, anticonvulsant action, spontaneous motor activity, and ethanol-potentiating action. Compounds 4d and 6d showed an inverse-agonist profile. These compounds were evaluated also for their binding at benzodiazepine site on GABAA receptor complex (GABAA/BzR complex) subtype to evaluate their subtype selectivity. 相似文献
78.
Rose G Romeo G Dato S Crocco P Bruni AC Hervonen A Majamaa K Sevini F Franceschi C Passarino G;GEnetics of Healthy Ageing Project Consortium 《PloS one》2010,5(10):e13395
Tissue specific somatic mutations occurring in the mtDNA control region have been proposed to provide a survival advantage. Data on twins and on relatives of long-lived subjects suggested that the occurrence/accumulation of these mutations may be genetically influenced. To further investigate control region somatic heteroplasmy in the elderly, we analyzed the segment surrounding the nt 150 position (previously reported as specific of Leukocytes) in various types of leukocytes obtained from 195 ultra-nonagenarians sib-pairs of Italian or Finnish origin collected in the frame of the GEHA Project. We found a significant correlation of the mtDNA control region heteroplasmy between sibs, confirming a genetic influence on this phenomenon. Furthermore, many subjects showed heteroplasmy due to mutations different from the C150T transition. In these cases heteroplasmy was correlated within sibpairs in Finnish and northern Italian samples, but not in southern Italians. This suggested that the genetic contribution to control region mutations may be population specific. Finally, we observed a possible correlation between heteroplasmy and Hand Grip strength, one of the best markers of physical performance and of mortality risk in the elderly. Our study provides new evidence on the relevance of mtDNA somatic mutations in aging and longevity and confirms that the occurrence of specific point mutations in the mtDNA control region may represent a strategy for the age-related remodelling of organismal functions. 相似文献
79.
WCI,a novel wheat chymotrypsin inhibitor: purification,primary structure,inhibitory properties and heterologous expression 总被引:1,自引:0,他引:1
Di Maro A Farisei F Panichi D Severino V Bruni N Ficca AG Ferranti P Capuzzi V Tedeschi F Poerio E 《Planta》2011,234(4):723-735
A novel chymotrypsin inhibitor, detected in the endosperm of Triticum aestivum, was purified and characterized with respect to the main physical–chemical properties. On the basis of its specificity, this
inhibitor was named WCI (wheat chymotrypsin inhibitor). WCI is a monomeric neutral protein made up of 119 residues and molecular
mass value of 12,933.40 Da. Automated sequence and mass spectrometry analyses, carried out on several samples of purified
inhibitor, evidenced an intrinsic molecular heterogeneity due to the presence of the isoform [des-(Thr)WCI], accounting for
about 40% of the total sample. In vitro, WCI acted as a strong inhibitor of bovine pancreatic chymotrypsin as well as of chymotryptic-like
activities isolated from the midgut of two phytophagous insects, Helicoverpa armigera (Hüb.) and Tenebrio molitor L., respectively. No inhibitory activities were detected against bacterial subtilisins, bovine pancreatic trypsin, porcine
pancreatic elastase or human leukocyte elastase. The primary structure of WCI was significantly similar (45.7–89.1%) to those
of several proteins belonging to the cereal trypsin/α-amylase inhibitor super-family and showed the typical sequence motif
of this crowed protein group. The cDNA of the inhibitor (wci-cDNA) was isolated from wheat immature caryopses and employed to obtain a recombinant product in E. coli. Experimental evidences indicated that the recombinant inhibitor was localized in the inclusion bodies from which it was
recovered as soluble and partially active protein by applying an appropriate refolding procedure. WCI reactive site localization,
as well as its inhibitory specificity, was investigated by molecular modeling approach. 相似文献
80.
D Rossi R Bruni N Bianchi C Chiarabelli R Gambari A Medici A Lista G Paganetto 《Phytomedicine》2003,10(2-3):139-144
Sangre de Drago is a red viscous latex extracted from Croton lechleri (Euphorbiaceae) cortex, renowned in South American popular medicine for its wound-healing properties. The in vitro antiproliferative effects were determined on the human myelogenous leukemia K562 cells line (IC50 = 2.5 +/- 0.3 microg ml(-1)). The mutagenic and antimutagenic activity of C. lechleri sap was examined by means of the Ames/Salmonella test. No mutagenic activity was found on the Salmonella typhimurium strains T98 and T100, either with or without S9 activation. On the other hand, the sap showed an inhibitory effect against the mutagenic activity of the indirectly acting mutagen 2-Aminoanthracene in presence of S9 and a moderate protective activity against directly acting mutagens Sodium Azide and 2-Nitrofluorene. Therefore we suggest that C. lechleri sap interacts with the enzymes of the S9 mix, thereby inhibiting the transformation of 2-Aminoantracene into its active forms. 相似文献