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161.
目的研究巨噬细胞移动抑制因子(MIF)在胰腺癌发生发展中的作用,与肿瘤标志物CEA、CA199的关系。方法应用免疫组化方法检测31例胰腺癌组织、癌旁组织以及14例正常胰腺组织中MIF表达水平,分析MIF表达与各项临床病理特点及血清CEA、CA199水平的关系。结果 MIF在胰腺癌组织中的表达为87.1%,高于癌旁组织的54.8%和正常胰腺组织的7.4%(P〈0.01);癌旁组织的MIF表达高于正常组织(P〈0.01)。MIF的表达与肿瘤分化程度及远处转移有关(P〈0.05),MIF表达阳性患者的血清CA199水平高于MIF表达阴性患者,而血清CEA水平两组间无显著统计学意义。结论 MIF对胰腺癌的发生发展起重要作用,可能促进正常腺体组织向胰腺癌发生和发展。MIF可作为胰腺癌的一种血清标志物,联合CA199的检测可更好的发现胰腺癌。 相似文献
162.
We have compared the ability of five Plasmodium falciparum microsatellites and three antigen-coding loci to differentiate recrudescence from reinfection. We used 133 pairs of P. falciparum-infected blood samples collected during in vivo drug efficacy trials from three sites in Kenya with different malaria endemicities. There were no significant differences between the marker subsets in their ability to discriminate recrudescences from new infections across the three sites. Overall, microsatellite loci revealed significantly higher expected heterozygosity and multiplicity of infection levels than antigen-coding loci. The mean expected heterozygosity across all loci in the three populations was significantly higher with microsatellites (0.70, 0.78 and 0.79) than antigen-coding loci (0.53, 0.60 and 0.62) for Mwea, Tiwi and Bondo areas, respectively. These observations can be explained by three non-exclusive hypotheses: (i) microsatellites are more polymorphic than antigenic loci; (ii) partially immune hosts remove certain parasites from infections on the basis of their antigenic alleles; and/or (iii) recombination occurs in vitro or in vivo with microsatellites. 相似文献
163.
Aditya K. Sanki Julie Boucau Donald R. Ronning Steven J. Sucheck 《Glycoconjugate journal》2009,26(5):589-596
Antigen 85 (ag85) is a complex of acyltransferases (ag85A–C) known to play a role in the mycolation of the d-arabino-d-galactan (AG) component of the mycobacterial cell wall. In order to better understand the chemistry and substrate specificity
of ag85, a trehalose monomycolate mimic p-nitrophenyl 6-O-octanoyl-β-d-glucopyranoside (1) containing an octanoyl moiety in lieu of a mycolyl moiety was synthesized as an acyl donor. Arabinofuranoside acceptors, methyl α-d-arabinofuranoside (2), methyl β-d-arabinofuranoside (3), and methyl 2-O-β-d-arabinofuranosyl-α-d-arabinofuranoside (9) were synthesized to mimic the terminal saccharides found on the AG. The acyl transfer reaction between acyl donor 1 and acceptors 2, 3, and 9 in the presence of ag85C from Mycobacterium tuberculosis (M. tuberculosis) resulted in the formation of esters, methyl 2, 5-di-O-octanoyl-α-d-arabinofuranoside (10), methyl 5-O-octanoyl-β-d-arabinofuranoside (11), and methyl 2-O-(5-O-octanoyl-β-d-arabinofuranosyl)-5-O-octanoyl-α-d-arabinofuranoside (12) in 2 h, 2 h and 8 h, respectively. The initial velocities of the reactions were determined with a newly developed assay
for acyltransferases. As expected, the regioselectivity corresponds to mycolylation patterns found at the terminus of the
AG in M. tuberculosis. The study shows that d-arabinose-based derivatives are capable of acting as substrates for ag85C-mediated acyl-transfer and the acyl glycoside 1 can be used in lieu of TMM extracted from bacteria to study ag85-mediated acyl-transfer and inhibition leading to the better understanding of
the ag85 protein class.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
164.
Godet Y Bonnin A Guilloux Y Vignard V Schadendorf D Dreno B Jotereau F Labarriere N 《Cancer immunology, immunotherapy : CII》2009,58(2):271-280
Melanoma reactive CTL were obtained by stimulating PBL from a melanoma patient in remission since 1994 following adjuvant
TIL immunotherapy, with the autologous melanoma cell line. They were cloned by limiting dilution. One CTL clone recognized
melanoma cell lines expressing tyrosinase and the B*4002 molecule, either spontaneously or upon transfection. We demonstrated
that this clone recognizes the tyrosinase-derived nonapeptide 316-324 (ADVEFCLSL) and the overlapping decapeptide 315–324
(SADVEFCLSL). We derived two distinct additional specific CTL clones from this same patient that were also reactive against
B*4002 melanoma cell lines, suggesting a relative diversity of this specific repertoire in this patient. Stimulating PBMC
derived from four additional B*4002 melanoma patients with the tyrosinase 316–324 nonapeptide induced the growth of specific
cells for two of the patients, demonstrating the immunogenicity of this new epitope. Our data show that this nonapeptide is
a new tool that could be used to generate melanoma-specific T cells for adoptive immunotherapy or serve as a peptide vaccine
for HLA-B*4002 melanoma patients. 相似文献
165.
Sylvie Rusakiewicz Geraldine Aubert Richard E. Clark Alejandro J. Madrigal Anthony I. Dodi Paul J. Travers 《Cancer immunology, immunotherapy : CII》2009,58(9):1459-1470
Soluble MHC–peptide complexes, commonly referred to as tetramers, have been shown to induce strong cross-linking of TCR and
CD8, resulting in a vigorous activation followed by a rapid non-apoptotic CD8+ T cell death. This has limited tetramer use for antigen-specific T cells isolation and cloning, as sorted tetramer positive
cells were shown to possess compromised functional integrity. Here we show that the cross-linking of a secondary co-stimulatory
signal into oligomeric MHC:peptide complexes prevents such cell death, and in contrast strongly stimulates antigen-specific
T cell responses. Such soluble antigen-presenting complexes (sAPCs) containing MHC:peptide complexes linked to either anti-CD27
or anti-CD28 antibodies were capable of priming and expanding HLA-A*0201 restricted CMV specific T cells and also of generating
functional HLA-A*0301 restricted BCR/ABL-specific T cell responses. These sAPCs constitute an encouraging alternative method
for generating antigen-specific T cells that could be applied to a variety of antigens.
A. I. Dodi and P. J. Travers contributed equally to this work.
This paper is an original contribution from the meeting which took place on 28 and 29 May 2008 in Nottingham, UK, celebrating
the contribution of Prof. I. A. “Tony” Dodi (†29.1.2008) to the EU project “Network for the identification and validation of antigens and biomarkers in cancer and their
application in clinical tumour immunology (ENACT)”. 相似文献
166.
Vujanovic L Whiteside TL Potter DM Chu J Ferrone S Butterfield LH 《Cancer immunology, immunotherapy : CII》2009,58(1):121-133
Recombinant adenoviral vectors (AdV) are potent vehicles for antigen engineering of dendritic cells (DC). DC engineered with
AdV to express full length tumor antigens are capable stimulators of antigen-specific polyclonal CD8+ and CD4+ T cells. To
determine the impact of AdV on the HLA class I antigen presentation pathway, we investigated the effects of AdV transduction
on antigen processing machinery (APM) components in human DC. Interactions among AdV transduction, maturation, APM regulation
and T cell activation were investigated. The phenotype and cytokine profile of DC transduced with AdV was intermediate, between
immature (iDC) and matured DC (mDC). Statistically significant increases in expression were observed for peptide transporters
TAP-1 and TAP-2, and HLA class I peptide-loading chaperone ERp57, as well as co-stimulatory surface molecule CD86 due to AdV
transduction. AdV transduction enhanced the expression of APM components and surface markers on mDC, and these changes were
further modulated by the timing of DC maturation. Engineering of matured DC to express a tumor-associated antigen stimulated
a broader repertoire of CD8+ T cells, capable of recognizing immunodominant and subdominant epitopes. These data identify
molecular changes in AdV-transduced DC (AdV/DC) that could influence T cell priming and should be considered in design of
cancer vaccines. 相似文献
167.
The prevalence of drug-resistant strains of Mycobacterium tuberculosis (M. tb) emphasizes the need for new antitubercular drugs. An essential component of the drug discovery process is the development of tools to rapidly screen potential drug libraries against important biological targets. Similarly to well-documented M. tb targets, the antigen 85 (Ag85) enzymes are involved in the maintenance of the mycobacterial cell wall. The products synthesized by these mycolyltransferases are the cell wall components most responsible for the reduced permeability of drugs into the bacterial cell, thereby linking Ag85 activity directly with drug resistance. This article presents the development of a high-throughput colorimetric assay suitable for direct monitoring of the enzymatic activity. The assay uses a synthetic substrate containing three chemical moieties: an octanoyl fatty acid, β-d-glucose, and p-nitrophenyl. In the context of the assay, Ag85 catalyzes the removal of the fatty acid and releases p-nitrophenyl-β-d-glucoside. The glucoside is hydrolyzed by β-glucosidase to release the p-nitrophenolate chromophore. With this assay, the KM and kcat values of Ag85C were determined to be 0.047 ± 0.008 mM and 0.062 s−1, respectively. In addition, the assay exhibits a Z′ value of 0.81 ± 0.06, indicating its suitability for high-throughput screening applications and drug development. 相似文献
168.
Vasileios A. Tatsis Ioannis G. Tsoulos Athanassios Stavrakoudis 《International journal of peptide research and therapeutics》2009,15(1):1-9
Humanized CAMPATH-1H antibody has been found to have biological applications through the recognition of the CD52 antigen.
A peptide mimotope of the CD52 antigen with the sequence T1SSPSAD7 has been co-crystallized with the CAMPATH-1H antibody. A plethora of hydrogen bond interactions were found to mediate antigen
recognition. An important feature of peptide’s bound conformation was the type I β-turn found in the S3PSA6 peptide’s fragment. Paradoxically, this fact has been underestimated from other researchers. In order to further investigate
the importance of this structural feature and its significance in antibody/antigen binding we have performed molecular dynamics
simulations in explicit water of the T1SSPSAD7 peptide in both antibody free and bound states. We have found that the turn structure has been perfectly retained in the
bound state but it was eliminated in the free state. This fact implies that the turn structure of the peptide is unstable
in aqueous environment and it is induced upon antibody binding. Analysis of the trajectories revealed also several other important
features of the antibody/antigen binding mode. 相似文献
169.
口蹄疫病毒单克隆抗体的制备及检测应用 总被引:3,自引:0,他引:3
用纯化的口蹄疫病毒(Footandmouthdiseasevirus,FMDV)免疫BALB/C小鼠,将免疫鼠的脾细胞与SP2/0骨髓瘤细胞融合,采用有限稀释法进行克隆,经筛选获得多株能稳定分泌抗FMDV单抗的杂交瘤细胞株。选择其中一株(2G12)用于下列实验,其细胞培养上清液的效价是1:256,腹水效价是1:1280;以自行制备的兔抗FMDV高免血清IgG为捕获抗体包被酶联免疫吸附试验微量反应板,以单抗2G12为第二抗体,建立了快速检测FMDV抗原的双抗体夹心ELISA,该方法能检出90ng病毒,而且只与FMDV发生特异性反应,与猪瘟病毒(HCV)、猪蓝耳病病毒(PRRSV)、伪狂犬病毒(PRV)、猪细小病毒(PPV)和乙脑病毒(JEV)均不发生反应。本研究为检测口蹄疫病毒抗原提供了灵敏和特异的方法。 相似文献
170.
Abhishek D. Garg Dominika Nowis Jakub Golab Peter Vandenabeele Dmitri V. Krysko Patrizia Agostinis 《生物化学与生物物理学报:癌评论》2010
Immunogenic profile of certain cancer cell death mechanisms has been transmuted by research published over a period of last few years and this change has been so drastic that a new (sub)class of apoptotic cancer cell death, redefined as ‘immunogenic apoptosis’ has started taking shape. In fact, it has been shown that this chemotherapeutic agent-specific immunogenic cancer cell death modality has the capabilities to induce ‘anticancer vaccine effect’, in vivo. These new trends have given an opportunity to combine tumour cell kill and antitumour immunity within a single paradigm, a sort of ‘holy grail’ of anticancer therapeutics. At the molecular level, it has been shown that the immunological silhouette of these cell death pathways is defined by a set of molecules called ‘damage-associated molecular patterns (DAMPs)’. Various intracellular molecules like calreticulin (CRT), heat-shock proteins (HSPs), high-mobility group box-1 (HMGB1) protein, have been shown to be DAMPs exposed/secreted in a stress agent/factor-and cell death-specific manner. These discoveries have motivated further research into discovery of new DAMPs, new pathways for their exposure/secretion, search for new agents capable of inducing immunogenic cell death and urge to solve currently present problems with this paradigm. We anticipate that this emerging amalgamation of DAMPs, immunogenic cell death and anticancer therapeutics may be the key towards squelching cancer-related mortalities, in near future. 相似文献