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941.
Marco Buscetta Salvatore Papasergi Arnaud Firon Giampiero Pietrocola Carmelo Biondo Giuseppe Mancuso Angelina Midiri Letizia Romeo Giuseppe Teti Pietro Speziale Patrick Trieu-Cuot Concetta Beninati 《The Journal of biological chemistry》2014,289(30):21003-21015
Streptococcus agalactiae (group B Streptococcus or GBS) is a common cause of invasive infections in newborn infants and adults. The ability of GBS to bind human fibrinogen is of crucial importance in promoting colonization and invasion of host barriers. We characterized here a novel fibrinogen-binding protein of GBS, designated FbsC (Gbs0791), which is encoded by the prototype GBS strain NEM316. FbsC, which bears two bacterial immunoglobulin-like tandem repeat domains and a C-terminal cell wall-anchoring motif (LPXTG), was found to be covalently linked to the cell wall by the housekeeping sortase A. Studies using recombinant FbsC indicated that it binds fibrinogen in a dose-dependent and saturable manner, and with moderate affinity. Expression of FbsC was detected in all clinical GBS isolates, except those belonging to the hypervirulent lineage ST17. Deletion of fbsC decreases NEM316 abilities to adhere to and invade human epithelial and endothelial cells, and to form biofilm in vitro. Notably, bacterial adhesion to fibrinogen and fibrinogen binding to bacterial cells were abolished following fbsC deletion in NEM316. Moreover, the virulence of the fbsC deletion mutant and its ability to colonize the brain were impaired in murine models of infection. Finally, immunization with recombinant FbsC significantly protected mice from lethal GBS challenge. In conclusion, FbsC is a novel fibrinogen-binding protein expressed by most GBS isolates that functions as a virulence factor by promoting invasion of epithelial and endothelial barriers. In addition, the protein has significant immunoprotective activity and may be a useful component of an anti-GBS vaccine. 相似文献
942.
Kali Janes Joshua W. Little Chao Li Leesa Bryant Collin Chen Zhoumou Chen Krzysztof Kamocki Timothy Doyle Ashley Snider Emanuela Esposito Salvatore Cuzzocrea Erhard Bieberich Lina Obeid Irina Petrache Grant Nicol William L. Neumann Daniela Salvemini 《The Journal of biological chemistry》2014,289(30):21082-21097
943.
Sai Li Christian Sieben Kai Ludwig Chris?T. H?fer Salvatore Chiantia Andreas Herrmann Frederic Eghiaian Iwan?A.T. Schaap 《Biophysical journal》2014,106(7):1447-1456
Upon endocytosis in its cellular host, influenza A virus transits via early to late endosomes. To efficiently release its genome, the composite viral shell must undergo significant structural rearrangement, but the exact sequence of events leading to viral uncoating remains largely speculative. In addition, no change in viral structure has ever been identified at the level of early endosomes, raising a question about their role. We performed AFM indentation on single viruses in conjunction with cellular assays under conditions that mimicked gradual acidification from early to late endosomes. We found that the release of the influenza genome requires sequential exposure to the pH of both early and late endosomes, with each step corresponding to changes in the virus mechanical response. Step 1 (pH 7.5–6) involves a modification of both hemagglutinin and the viral lumen and is reversible, whereas Step 2 (pH <6.0) involves M1 dissociation and major hemagglutinin conformational changes and is irreversible. Bypassing the early-endosomal pH step or blocking the envelope proton channel M2 precludes proper genome release and efficient infection, illustrating the importance of viral lumen acidification during the early endosomal residence for influenza virus infection. 相似文献
944.
945.
Binding of azurin to cytochrome c 551 as investigated by surface plasmon resonance and fluorescence
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Simona Santini Anna Rita Bizzarri Tohru Yamada Craig W. Beattie Salvatore Cannistraro 《Journal of molecular recognition : JMR》2014,27(3):124-130
The interaction between azurin (Az) and cytochrome c 551 (CytC551) from Pseudomonas aeruginosa deserves particular interest for both its physiological aspects and their possible applications in bionano devices. Here, the kinetics of the interaction has been studied by surface plasmon resonance and fluorescence quenching. Surface plasmon resonance data have been successfully interpreted by the heterogeneous ligand model, which predicts the existence of two binding sites on the immobilized Az for CytC551 molecules in solution. On the other hand, the fluorescence study indicates the formation of a complex, with the involvement of the lone Az tryptophan (Trp) at position 48. The two different techniques point out the occurrence of an encounter complex between Az and CytC551 that evolves toward the formation of a more stable complex characterized by an equilibrium dissociation constant KD typical of transient interactions. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
946.
947.
Barbara Lombardo Carlo Ceglia Marina Tarsitano Ippolito Pierucci Francesco Salvatore Lucio Pastore 《Gene》2014
We evaluated a patient, born after a normal 38-week pregnancy, with psychomotor retardation, poor coordination of ocular movements, recurrent vomiting and severe lactic acidosis. The patient was admitted to hospital at 2 months of age because of a mitochondrial-like syndrome and died at the age of 4.5 months. Array-comparative genomic hybridization (a-CGH) analysis revealed a homozygous deletion in 5q11.2 involving NADH dehydrogenase (ubiquinone) Fe–S protein 4, 18 kDa (NADH-coenzyme Q reductase; NDUFS4). Both parents were heterozygous for the mutation. The array revealed a deletion of ~ 32 kb that includes exon 2 of NDUFS4 subsequently confirmed by real time-PCR and multiplex PCR. NDUFS4 was previously correlated to Leigh syndrome since mutations in this gene block the assembly of complex I. This result demonstrates the relevance of a-CGH screening in patients affected by metabolic disorders of unknown etiology. 相似文献
948.
Tonino Ercolino Roberta Lai Valentino Giachè Salvatore Melchionda Massimo Carella Alessandro Delitala Massimo Mannelli Giuseppe Fanciulli 《Gene》2014
Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disease with an estimated incidence of 1 in 3000/3500 live births. NF1 is caused by a mutation in a gene which encodes a protein known as neurofibromin. In up to 5% of cases, NF1 is associated with pheochromocytomas. 相似文献
949.
We have previously reported that nickel acetate (Ni2+), a well-known human carcinogenic agents, differentially affected apoptosis in two different airway epithelial cell lines derived from the human respiratory tract (A549 and Beas-2B, respectively), suggesting a potential involvement of epidermal growth factor receptor (EGFR)/Neu receptors in mediating this effect. Since ErbBs are closely associated to Mucin 1 (MUC1), a glycoprotein component of airway mucus that is overexpressed in lung tumors, we have investigated the role of this signaling system in the survival response of airway epithelial cells against Ni2+-induced cell death. We found that A549 cells exposed to Ni2+ do not show any significant increase of MUC1 levels. Conversely, Beas-2B cells exposed to equivalent concentrations of Ni2+ showed increased expression of MUC1 levels and this correlated with increased phosphorylation of both EGFR and of the extracellular-regulated kinase 1/2 (ERK1/2) and increase resistance to apoptosis, as indicated by cell viability assessments and DNA damage. Interestingly, suppression of MUC1 by small interfering RNA inhibited the EGFR activation in Beas-2B cells, leading to a significant decrease of survival and enhancement of DNA fragmentation and cleaved Caspase-3 expression. These results strongly suggest a role for MUC1 in Ni2+-induced neoplastic transformation, which likely involves the activation of the EGFR-mediated cell survival pathway, highlighting new avenues in the molecular approach to lung cancer prevention. 相似文献
950.
研究发现,取自蓝铜蛋白azurin的一段多肽p28能够进入癌细胞,结合到肿瘤抑制因子p53的DNA结合域上,进而增加p53的抗癌能力.本工作中,通过拉伸分子动力学方法,在原子尺度上研究了p28-p53 DBD复合物的解离过程.分析结果显示复合物的解离过程遵循着一定的分离顺序.对解离力的分析以及对沿着解离路径的不可逆做功的计算,使我们能够从复合物的能量地貌中提取有用的信息,而这些信息也决定了复合物的解离过程. 相似文献