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91.
92.
Expression of distinct conformations of free HLA-Cw4 heavy chains in transfected neuroblastoma cells
Anna Marozzi Raffaella Meneveri Claudio De Santis Piera Robbioni Elena Molteni Alberto Beretta Antonio G. Siccardi Enrico Ginelli 《Immunogenetics》1996,43(5):289-295
Epitope mapping of HLA-Cw4 indicates that the two monoclonal antibodies (mAbs) L31 and M38, specific for beta 2-microglobulin
(β2m)-free HLA-C heavy chains, react preferentially with the KYK motif, located in the binding groove (α1 domain). Transfection
of HLA-Cw4 cDNA into a neuroblastoma cell line, which normally expresses negligible HLA class I, resulted in the constitutive
surface expression of molecules displaying different reactivities with the two mAbs. This cellular system was used to determine
whether L31 and M38 recognize distinct conformations of β2m-free HLA-C proteins, and to investigate their mechanism of expression. Interferon-γ greatly enhanced the expression of L31-reactive
free chains, while abolishing that of M38-reactive molecules. The cytokine-induced expression of L31-reactive molecules was
inhibited by anti-sense oligonucleotides specific for β2m mRNA, while constitutive expression of L31-reactive molecules was only partially affected. Exogenous β2m resulted in a reduction of constitutive L31 reactivity, and in a concomitant increase of M38 reactivity. These results indicate
that: 1) at the cell surface, L31 and M38 react with two distinct conformations of HLA-Cw4 β2m-free heavy chains, of which the L31-reactive conformation is the least folded; 2) the expression of both conformers can
be modulated by endogenous or exogenous β2m; and (3) L31-reactive molecules exposed at the cell surface are likely to derive from the dissociation of empty HLA-Cw4/β2m complexes. 相似文献
93.
Silvia Revelli Hector Davila Maria E. Ferro Marta Romero-Piffiguer Orlando Musso Jose Valenti Jorge Bernabo Ernesto Falcoff Jeanne Wietzerbin Oscar Bottasso 《Microbiology and immunology》1995,39(4):275-281
We examined the effects of recombinant rat inteferon-gamma (IFN-γ) injections on the parasitologic, serologic, immunologic and histopathologic features of acute and chronic experimental Trypanosoma cruzi (T. cruzi) infections in “l” rats. Upon infection at weaning, two rat groups were allocated to receive a 20-day cycle of IFN-γ injections, 20,000 IU/rat each, which started at 1, and 7 days post-infection (pi). Treatment with IFN-γ, initiated at either 1 or 7 days pi, resulted in comparatively lower peak parasitemias (P<0.02) but in similar levels of anti-T. cruzi circulating antibodies and serum IFN-γ activities. The latter appeared significantly increased during acute infection whereas biologically active tumor necrosis factor was virtually undetectable in serum from infected rats regardless of whether they had been given IFN-γ or not. The prevalence of chronic focal myocarditis in IFN-γ-treated infected rats showed no differences with respect to the one recorded in control-infected counterparts. The inverse CD4/CD8 ratio of spleen and lymph node T cells that usually accompanies chronic infection was reversed by IFN-γ. Mononuclear cells carrying class III-A and I-E molecules, that were found to have increased at both compartments, appeared also modified upon IFN-γ treatment with an overincrease of I-A-positive cells, and a normalization of I-E-bearing cells. 相似文献
94.
95.
The aim of this work is to study the binding of nickel ions to hexahistidine (His(6)) combining potentiometric titrations and spectroscopic (UV-Vis and circular dichroism) determinations in order to establish the species distribution as a function of the pH, their stoichiometry, stability and geometry. For comparative purposes, the same procedure was applied to the Ni-histidine (His) system. His behaves as a tridentate ligand, coordinating the carboxyl group, the imidazole and the amino nitrogen atoms to Ni(II) ions in an octahedral coordination and a bis(histidine) complex is formed at pH higher than 5. For the Ni-His(6) system, the complex formation starts at pH 4 and five different species (Ni(His(6))H, Ni(His(6)), Ni(n)(His(6))(n), Ni(n)(His(6))(n)H(-n/2), Ni(n)(His(6))(n)H(-n)) are formed as a function of the pH. Ni(His(6))H involves the coordination of the imidazole nitrogen and a deprotonated amide nitrogen (N(Im), N(-)) resulting in an octahedral geometry. In Ni(His(6)), an imidazole nitrogen is deprotonated and coordinated (2N(Im), N(-)) to the metal ion with a square planar geometry. The aggregated forms result from the extra Ni-N(Im) coordination, resulting in a 4N square planar geometry that is stabilized by inter/intramolecular hydrogen bonds. This coordination mode is not altered during the deprotonation steps from Ni(n)(His(6))(n). 相似文献
96.
Auinger A Valenti L Pfeuffer M Helwig U Herrmann J Fracanzani AL Dongiovanni P Fargion S Schrezenmeir J Rubin D 《Hormones et métabolisme》2010,42(12):854-859
The fatty acid transport protein 5 (FATP5) is exclusively expressed in the liver and is involved in hepatic lipid and bile metabolism. We investigated whether a variation in the FATP5 promoter (rs56225452) is associated with hepatic steatosis and further features of the metabolic syndrome. A total of 716 male subjects from the Metabolic Intervention Cohort Kiel (MICK) and 103 male subjects with histologically proved nonalcoholic fatty liver disease (NAFLD) were genotyped for this FATP5 polymorphism rs56225452 and phenotyped for features of the metabolic syndrome. In the MICK cohort, ALT activities, postprandial insulin, and triglyceride concentrations were higher in subjects carrying the rare A-allele compared to GG homozygotes. Accordingly, the insulin sensitivity index determined after a mixed meal and standardized glucose load was lower in A-allele carriers. NAFLD cases carrying allele A were presented with also higher ALT activities. In NAFLD subjects, the association of BMI with the degree of steatosis and glucose concentration differed across FATP5 promoter polymorphism. The FATP5 promoter polymorphism rs56225452 is associated with higher ALT activity, insulin resistance, and dyslipidemia in the general population. The impact of the BMI on the severity of steatosis in NAFLD cases seems to depend on the FATP5 polymorphism. 相似文献
97.
Kamath AT Rochat AF Valenti MP Agger EM Lingnau K Andersen P Lambert PH Siegrist CA 《PloS one》2008,3(11):e3683
Background
With the exception of some live vaccines, e.g. BCG, subunit vaccines formulated with “classical” adjuvants do not induce similar responses in neonates as in adults. The usual neonatal profile is characterized by lower levels of TH1-associated biomarkers. This has hampered the development of new neonatal vaccines for diseases that require early protection. Tuberculosis is one of the major targets for neonatal immunization. In this study, we assessed the immunogenicity of a novel candidate vaccine comprising a mycobacterial fusion protein, Ag85B-ESAT-6, in a neonatal murine immunization model.Methods/Findings
The Ag85B-ESAT-6 fusion protein was formulated either with a classical alum based adjuvant or with the novel IC31® adjuvant. Following neonatal or adult immunization, 3 parameters were studied in vivo: (1) CD4+ T cell responses, (2) vaccine targeting/activation of dendritic cells (DC) and (3) protection in a surrogate mycobacterial challenge model. Conversely to Alum, IC31® induced in both age groups strong Th1 and Th17 responses, characterized by multifunctional T cells expressing IL-2 and TNF-α with or without IFN-γ. In the draining lymph nodes, a similarly small number of DC contained the adjuvant and/or the antigen following neonatal or adult immunization. Expression of CD40, CD80, CD86 and IL-12p40 production was focused on the minute adjuvant-bearing DC population. Again, DC targeting/activation was similar in adults and neonates. These DC/T cell responses resulted in an equivalent reduction of bacterial growth following infection with M. bovis BCG, whereas no protection was observed when Alum was used as adjuvant.Conclusion
Neonatal immunization with the IC31®- adjuvanted Ag85B-ESAT-6 subunit vaccine elicited adult-like multifunctional protective anti-mycobacterial T cell responses through the induction of an adult pattern of in vivo DC activation. 相似文献98.
Marianna Rossetti Rosa Merlo Neda Bagheri Danila Moscone Anna Valenti Aakash Saha Pablo
R Arantes Rudy Ippodrino Francesco Ricci Ida Treglia Elisabetta Delibato John van
der
Oost Giulia Palermo Giuseppe Perugino Alessandro Porchetta 《Nucleic acids research》2022,50(14):8377
The RNA programmed non-specific (trans) nuclease activity of CRISPR-Cas Type V and VI systems has opened a new era in the field of nucleic acid-based detection. Here, we report on the enhancement of trans-cleavage activity of Cas12a enzymes using hairpin DNA sequences as FRET-based reporters. We discover faster rate of trans-cleavage activity of Cas12a due to its improved affinity (Km) for hairpin DNA structures, and provide mechanistic insights of our findings through Molecular Dynamics simulations. Using hairpin DNA probes we significantly enhance FRET-based signal transduction compared to the widely used linear single stranded DNA reporters. Our signal transduction enables faster detection of clinically relevant double stranded DNA targets with improved sensitivity and specificity either in the presence or in the absence of an upstream pre-amplification step. 相似文献
99.
Antiviral activity of ovotransferrin discloses an evolutionary strategy for the defensive activities of lactoferrin. 总被引:7,自引:0,他引:7
Francesco Giansanti Paola Rossi Maria Teresa Massucci Dario Botti Giovanni Antonini Piera Valenti Lucilla Seganti 《Biochimie et biologie cellulaire》2002,80(1):125-130
Ovotransferrin (formerly conalbumin) is an iron-binding protein present in birds. It belongs to the transferrin family and shows about 50% sequence homology with mammalian serum transferrin and lactoferrin. This protein has been demonstrated to be capable of delivering iron to cells and of inhibiting bacterial multiplication. However, no antiviral activity has been reported for ovotransferrin, although the antiviral activity of human and bovine lactoferrins against several viruses, including human herpes simplex viruses, has been well established. In this report, the antiviral activity of ovotransferrin towards chicken embryo fibroblast infection by Marek's disease virus (MDV), an avian herpesvirus, was clearly demonstrated. Ovotransferrin was more effective than human and bovine lactoferrins in inhibiting MDV infection and no correlation between antiviral efficacy and iron saturation was found. The observations reported here are of interest from an evolutionary point of view since it is likely that the defensive properties of transferrins appeared early in evolution. In birds, the defensive properties of ovotransferrin remained joined to iron transport functions; in mammals, iron transport functions became peculiar to serum transferrin, and the defensive properties towards infections were optimised in lactoferrin. 相似文献
100.
Giuseppe Perugino Riccardo Miggiano Mario Serpe Antonella Vettone Anna Valenti Samarpita Lahiri Franca Rossi Mosè Rossi Menico Rizzi Maria Ciaramella 《Nucleic acids research》2015,43(18):8801-8816
Alkylated DNA-protein alkyltransferases repair alkylated DNA bases, which are among the most common DNA lesions, and are evolutionary conserved, from prokaryotes to higher eukaryotes. The human ortholog, hAGT, is involved in resistance to alkylating chemotherapy drugs. We report here on the alkylated DNA-protein alkyltransferase, SsOGT, from an archaeal species living at high temperature, a condition that enhances the harmful effect of DNA alkylation. The exceptionally high stability of SsOGT gave us the unique opportunity to perform structural and biochemical analysis of a protein of this class in its post-reaction form. This analysis, along with those performed on SsOGT in its ligand-free and DNA-bound forms, provides insights in the structure-function relationships of the protein before, during and after DNA repair, suggesting a molecular basis for DNA recognition, catalytic activity and protein post-reaction fate, and giving hints on the mechanism of alkylation-induced inactivation of this class of proteins. 相似文献