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81.
Dallavalle S Rocchetta DG Musso L Merlini L Morini G Penco S Tinelli S Beretta GL Zunino F 《Bioorganic & medicinal chemistry letters》2008,18(9):2781-2787
A series of novel 9-substituted camptothecins derived from 9-formylcamptothecin were synthesized. The aldehyde was obtained from 10-hydroxycamptothecin or, better, by total synthesis. The compounds showed antiproliferative activity higher than that of the reference compound topotecan. Modelling suggested the possibility of a favourable interaction of small and polar 9-substituents with the topoisomerase I–DNA complex, which is consistent with the higher activity of these derivatives with respect to the corresponding 7-substituted camptothecins. 相似文献
82.
M A Findeis G M Musso C C Arico-Muendel H W Benjamin A M Hundal J J Lee J Chin M Kelley J Wakefield N J Hayward S M Molineaux 《Biochemistry》1999,38(21):6791-6800
Cellular toxicity resulting from nucleation-dependent polymerization of amyloid beta-peptide (Abeta) is considered to be a major and possibly the primary component of Alzheimer's disease (AD). Inhibition of Abeta polymerization has thus been identified as a target for the development of therapeutic agents for the treatment of AD. The intrinsic affinity of Abeta for itself suggested that Abeta-specific interactions could be adapted to the development of compounds that would bind to Abeta and prevent it from polymerizing. Abeta-derived peptides of fifteen residues were found to be inhibitory of Abeta polymerization. The activity of these peptides was subsequently enhanced through modification of their amino termini with specific organic reagents. Additional series of compounds prepared to probe structural requirements for activity allowed reduction of the size of the inhibitors and optimization of the Abeta-derived peptide portion to afford a lead compound, cholyl-Leu-Val-Phe-Phe-Ala-OH (PPI-368), with potent polymerization inhibitory activity but limited biochemical stability. The corresponding all-D-amino acyl analogue peptide acid (PPI-433) and amide (PPI-457) retained inhibitory activity and were both stable in monkey cerebrospinal fluid for 24 h. 相似文献
83.
84.
Dr. Edward B. Blanchard Robert J. McCaffrey Alison Musso Maryrose A. Gerardi Guy C. McCoy 《Applied psychophysiology and biofeedback》1987,12(3):227-240
Eighty-seven medicated essential hypertensives received either thermal biofeedback (TBF) or progressive muscle relaxation (PMR) training as a substitute for their second-stage antihypertensive medication. The psychological changes accompanying the treatments were obtained at pretreatment, at post-treatment and at the 3- and 6-month follow-up. Few psychological changes were noted, owing in part to the absence of psychopathological elevations at pretreatment. Short-term psychological changes were greater in patients who were withdrawn from their second-stage antihypertensive medication and then treated compared with those treated and then withdrawn from their medication. This finding may reflect the presence of antihypertensive medication side effects involving psychological factors. In general, TBF patients were more Type B at long-term follow-up compared with PMR patients, who tended toward greater Type A characteristics.This research was supported by a grant from NHLBI, HL-27622. 相似文献
85.
Apple production and quality when cultivated under anti-hail cover in Southern Brazil 总被引:1,自引:0,他引:1
86.
Carmen Parola Laura Salogni Xenia Vaira Sara Scutera Paolo Somma Valentina Salvi Tiziana Musso Giuseppe Tabbia Marco Bardessono Christian Pasquali Alberto Mantovani Silvano Sozzani Daniela Bosisio 《PloS one》2013,8(12)
OM-85 (Broncho-Vaxom®, Broncho-Munal®, Ommunal®, Paxoral®, Vaxoral®), a product made of the water soluble fractions of 21 inactivated bacterial strain patterns responsible for respiratory tract infections, is used for the prevention of recurrent upper respiratory tract infections and acute exacerbations in chronic obstructive pulmonary disease patients. OM-85 is able to potentiate both innate and adaptive immune responses. However, the molecular mechanisms responsible for OM-85 activation are still largely unknown. Purpose of this study was to investigate the impact of OM-85 stimulation on human dendritic cell functions. We show that OM-85 selectively induced NF-kB and MAPK activation in human DC with no detectable action on the interferon regulatory factor (IRF) pathway. As a consequence, chemokines (i.e. CXCL8, CXCL6, CCL3, CCL20, CCL22) and B-cell activating cytokines (i.e. IL-6, BAFF and IL-10) were strongly upregulated. OM-85 also synergized with the action of classical pro-inflammatory stimuli used at suboptimal concentrations. Peripheral blood mononuclear cells from patients with COPD, a pathological condition often associated with altered PRR expression pattern, fully retained the capability to respond to OM-85. These results provide new insights on the molecular mechanisms of OM-85 activation of the immune response and strengthen the rational for its use in clinical settings. 相似文献
87.
Bocchi L Savi M Graiani G Rossi S Agnetti A Stillitano F Lagrasta C Baruffi S Berni R Frati C Vassalle M Squarcia U Cerbai E Macchi E Stilli D Quaini F Musso E 《PloS one》2011,6(3):e17750
Heart repair by stem cell treatment may involve life-threatening arrhythmias. Cardiac progenitor cells (CPCs) appear best suited for reconstituting lost myocardium without posing arrhythmic risks, being commissioned towards cardiac phenotype. In this study we tested the hypothesis that mobilization of CPCs through locally delivered Hepatocyte Growth Factor and Insulin-Like Growth Factor-1 to heal chronic myocardial infarction (MI), lowers the proneness to arrhythmias. We used 133 adult male Wistar rats either with one-month old MI and treated with growth factors (GFs, n = 60) or vehicle (V, n = 55), or sham operated (n = 18). In selected groups of animals, prior to and two weeks after GF/V delivery, we evaluated stress-induced ventricular arrhythmias by telemetry-ECG, cardiac mechanics by echocardiography, and ventricular excitability, conduction velocity and refractoriness by epicardial multiple-lead recording. Invasive hemodynamic measurements were performed before sacrifice and eventually the hearts were subjected to anatomical, morphometric, immunohistochemical, and molecular biology analyses. When compared with untreated MI, GFs decreased stress-induced arrhythmias and concurrently prolonged the effective refractory period (ERP) without affecting neither the duration of ventricular repolarization, as suggested by measurements of QTc interval and mRNA levels for K-channel α-subunits Kv4.2 and Kv4.3, nor the dispersion of refractoriness. Further, markers of cardiomyocyte reactive hypertrophy, including mRNA levels for K-channel α-subunit Kv1.4 and β-subunit KChIP2, interstitial fibrosis and negative structural remodeling were significantly reduced in peri-infarcted/remote ventricular myocardium. Finally, analyses of BrdU incorporation and distribution of connexin43 and N-cadherin indicated that cytokines generated new vessels and electromechanically-connected myocytes and abolished the correlation of infarct size with deterioration of mechanical function. In conclusion, local injection of GFs ameliorates electromechanical competence in chronic MI. Reduced arrhythmogenesis is attributable to prolongation of ERP resulting from improved intercellular coupling via increased expression of connexin43, and attenuation of unfavorable remodeling. 相似文献
88.
Cao-Lormeau VM Roche C Aubry M Teissier A Lastere S Daudens E Mallet HP Musso D Aaskov J 《PloS one》2011,6(12):e29555
Background
Infection by dengue virus (DENV) is a major public health concern in hundreds of tropical and subtropical countries. French Polynesia (FP) regularly experiences epidemics that initiate, or are consecutive to, DENV circulation in other South Pacific Island Countries (SPICs). In January 2009, after a decade of serotype 1 (DENV-1) circulation, the first cases of DENV-4 infection were reported in FP. Two months later a new epidemic emerged, occurring about 20 years after the previous circulation of DENV-4 in FP. In this study, we investigated the epidemiological and molecular characteristics of the introduction, spread and genetic microevolution of DENV-4 in FP.Methodology/Principal Findings
Epidemiological data suggested that recent transmission of DENV-4 in FP started in the Leeward Islands and this serotype quickly displaced DENV-1 throughout FP. Phylogenetic analyses of the nucleotide sequences of the envelope (E) gene of 64 DENV-4 strains collected in FP in the 1980s and in 2009–2010, and some additional strains from other SPICs showed that DENV-4 strains from the SPICs were distributed into genotypes IIa and IIb. Recent FP strains were distributed into two clusters, each comprising viruses from other but distinct SPICs, suggesting that emergence of DENV-4 in FP in 2009 resulted from multiple introductions. Otherwise, we observed that almost all strains collected in the SPICs in the 1980s exhibit an amino acid (aa) substitution V287I within domain I of the E protein, and all recent South Pacific strains exhibit a T365I substitution within domain III.Conclusions/Significance
This study confirmed the cyclic re-emergence and displacement of DENV serotypes in FP. Otherwise, our results showed that specific aa substitutions on the E protein were present on all DENV-4 strains circulating in SPICs. These substitutions probably acquired and subsequently conserved could reflect a founder effect to be associated with epidemiological, geographical, eco-biological and social specificities in SPICs. 相似文献89.
90.
Musso Munyeme John B Muma Hetron M Munang'andu Clovice Kankya Eystein Skjerve Morten Tryland 《BMC veterinary research》2010,6(1):21