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151.
Xiaofei Chang Eugene Izumchenko Luisa M. Solis Myoung Sook Kim Aditi Chatterjee Shizhang Ling Constance L. Monitto Paul M. Harari Manuel Hidalgo Steve N. Goodman Ignacio I. Wistuba Atul Bedi David Sidransky 《PloS one》2013,8(7)
The sensitivity of only a few tumors to anti-epidermal growth factor receptor EGFR tyrosine kinase inhibitors (TKIs) can be explained by the presence of EGFR tyrosine kinase (TK) domain mutations. In addition, such mutations were rarely found in tumor types other than lung, such as pancreatic and head and neck cancer. In this study we sought to elucidate mechanisms of resistance to EGFR-targeted therapies in tumors that do not harbor TK sensitizing mutations in order to identify markers capable of guiding the decision to incorporate these drugs into chemotherapeutic regimens. Here we show that EGFR activity was markedly decreased during the evolution of resistance to the EGFR tyrosine kinase inhibitor (TKI) erlotinib, with a concomitant increase of mitogen-inducible gene 6 (Mig6), a negative regulator of EGFR through the upregulation of the PI3K-AKT pathway. EGFR activity, which was more accurately predicted by the ratio of Mig6/EGFR, highly correlated with erlotinib sensitivity in panels of cancer cell lines of different tissue origins. Blinded testing and analysis in a prospectively followed cohort of lung cancer patients treated with gefitinib alone demonstrated higher response rates and a marked increased in progression free survival for patients with a low Mig6/EGFR ratio (approximately 100 days, P = 0.01). 相似文献
152.
Scavenging of superoxide radical by ascorbic acid 总被引:1,自引:0,他引:1
Using acetaldehyde and xanthine oxidase as the source of suPeroxide radical, the second order rate constant for the reaction
between ascorbic acid and superoxide radical was estimated to be 8.2 X 107 M-1 s-1. In rats, the average tissue concentration of ascorbic acid was of the order of 10-3 M and that of superoxide dismutase was of the order of 10-6 M. So, taking together both the rate constants and the tissue concentrations, the efficacy of ascorbic acid for scavenging
superoxide radical in animal tissues appears to be better than that of suPeroxide dismutase. The significance of ascorbic
acid as a scavenger of superoxide radical has been discussed from the point of view of the evolution of ascorbic acid synthesizing
capacity of terrestrial vertebrates. 相似文献
153.
154.
155.
Oxyhaemoglobins from erythrocytes of different animals including fish, amphibians, reptiles, birds, mammals and human beings
have been isolated by ion-exchange chromatography over phosphocellulose and the comparative rates of autoxidation of oxyhaemoglobin
studied. The mechanism of autoxidationin vitro has been elucidated using toad as well as human oxyhaemoglobin. Autoxidation is markedly inhibited by carbon monoxide as
well as by anion ligands, namely, potassium cyanide, sodium azide and potassium thiocyanate. The inhibition by anions is in
the same order as their strength as nucleophiles, indicating that it is the oxyhaemoglobin and not the ligand-bound deoxy
species which undergoes autoxidation. The structure of oxyhaemoglobin is considered to be mainly
and determination of the rate of autoxidation with or without using superoxide dismutase and catalase indicates that the
initial process of autoxidation takes place by dissociation of
to methaemoglobin and superoxide to the extent of 24%. The superoxide thus produced reattacks oxyhaemoglobin to produce further
methaemoglobin and hydrogen peroxide. H2O2 is a major oxidant of oxyhaemoglobin producing methaemoglobin to the extent of 53%. A tentative mechanism of autoxidation
showing the sequence of reactions involving superoxide, H2O2 and OH has been presented. 相似文献
156.
Previously it was shown that the Aspergillus nidulans (A.n.) mitochondrial COB intron maturase, I-AniI, facilitates splicing of the COB intron in vitro. In this study, we apply kinetic analysis of binding and splicing along with RNA deletion analysis to gain insight into the mechanism of I-AniI facilitated splicing. Our results are consistent with I-AniI and A.n. COB pre-RNA forming a specific but labile encounter complex that is resolved into the native, splicing-competent complex. Significantly, kinetic analysis of splicing shows that the resolution step is rate limiting for splicing. RNA deletion studies show that I-AniI requires most of the A.n. COB intron for binding suggesting that the integrity of the I-AniI-binding site depends on overall RNA tertiary structure. These results, taken together with the observation that A.n. COB intron lacks significant stable tertiary structure in the absence of protein, support a model in which I-AniI preassociates with an unfolded COB intron via a "labile" interaction that facilitates correct folding of the intron catalytic core, perhaps by resolving misfolded RNAs or narrowing the number of conformations sampled by the intron during its search for native structure. The active intron conformation is then "locked in" by specific binding of I-Anil to its intron interaction site. 相似文献
157.
Chatterjee S Sankaranarayanan R Sonti RV 《Molecular plant-microbe interactions : MPMI》2003,16(11):973-982
Xanthomonas oryzae pv. oryzae causes bacterial leaf blight, a serious disease of rice. We have identified a novel virulence deficient mutant (BXO1691) of X. oryzae pv. oryzae that has a Tn5 insertion in an open reading frame (phyA; putative phytase A) encoding a 373-amino acid (aa) protein containing a 28-aa predicted signal peptide. Extracellular protein profiles revealed that a 38-kDa band is absent in phyA mutants as compared with phyA+ strains. A BLAST search with phyA and its deduced polypeptide sequence indicated significant similarity with conserved hypothetical proteins in Xanthomonas axonopodis pv. citri and Xanthomonas campestris pv. campestris and limited homology to secreted phytases of Bacillus species. Homology modeling with a Bacillus phytase as the template suggests that the PhyA protein has a similar six-bladed beta-propeller architecture and exhibits conservation of certain critical active site residues. Phytases are enzymes that are involved in degradation of phytic acid (inositol hexaphosphate), a stored form of phosphate in plants. The phyA mutants exhibit a growth deficiency in media containing phytic acid as a sole phosphate source. Exogenous phosphate supplementation promotes migration of phyA X. oryzae pv. oryzae mutants in rice leaves. These results suggest that the virulence deficiency of phyA mutants is, at least in part, due to inability to use host phytic acid as a source of phosphate. phyA-like genes have not been previously reported to be involved in the virulence of any plant pathogenic bacterium. 相似文献
158.
Madhu Beta Vikas Khetan Nivedita Chatterjee Ganesan Suganeswari Pukhraj Rishi Jyotirmay Biswas Subramanian Krishnakumar 《PloS one》2014,9(12)
The co-ordinated regulation of oncogenes along with miRNAs play crucial role in carcinogenesis. In retinoblastoma (RB), several miRNAs are known to be differentially expressed. Epithelial cell adhesion molecule (EpCAM) gene is involved in many epithelial cancers including, retinoblastoma (RB) tumorigenesis. EpCAM silencing effectively reduces the oncogenic miR-17-92 cluster. In order to investigate whether EpCAM has wider effect as an inducer or silencer of miRNAs, we performed a global microRNA expression profile in EpCAM siRNA knockdown Y79 cells. MicroRNA profiling in EpCAM silenced Y79 cells showed seventy-three significantly up regulated and thirty-six down regulated miRNAs. A subset of these miRNAs was also validated in tumors. Functional studies on Y79 and WERI-Rb-1 cells transfected with antagomirs against two miRNAs of miR-181c and miR-130b showed striking changes in tumor cell properties in RB cells. Treatment with anti-miR-181c and miR-130b showed significant decrease in cell viability and cell invasion. Increase in caspase-3 level was noticed in antagomir transfected cell lines indicating the induction of apoptosis. Possible genes altered by EpCAM influenced microRNAs were predicted by bioinformatic tools. Many of these belong to pathways implicated in cancer. The study shows significant influence of EpCAM on global microRNA expression. EpCAM regulated miR-181c and miR-130b may play significant roles in RB progression. EpCAM based targeted therapies may reduce carcinogenesis through several miRNAs and target genes. 相似文献
159.
Mader M de Dios A Shih C Bonjouklian R Li T White W López de Uralde B Sánchez-Martinez C del Prado M Jaramillo C de Diego E Martín Cabrejas LM Dominguez C Montero C Shepherd T Dally R Toth JE Chatterjee A Pleite S Blanco-Urgoiti J Perez L Barberis M Lorite MJ Jambrina E Nevill CR Lee PA Schultz RC Wolos JA Li LC Campbell RM Anderson BD 《Bioorganic & medicinal chemistry letters》2008,18(1):179-183
Herein we report investigations into the p38alpha MAP kinase activity of trisubstituted imidazoles that led to the identification of compounds possessing highly potent in vivo activity. The SAR of a novel series of imidazopyridines is demonstrated as well, resulting in compounds possessing cellular potency and enhanced in vivo activity in the rat collagen-induced arthritis model of chronic inflammation. 相似文献
160.
James W. Freeman Amitava Chatterjee Brenda E. Ross Harris Busch 《Molecular and cellular biochemistry》1985,68(1):87-96
Summary Extractable nucleolar proteins from HeLa cells were used as a source of antigen to immunize mice for monoclonal antibody (MAb) production. Ten of the resulting MAbs shown to identify nucleolar phosphoprotein (110 kD/pI 5.5) were purified and used in immunochemical studies to further characterize protein C23. All ten MAbs showed nucleolar localization by indirect immunofluorescence; one antibody (FR2) also showed some nucleoplasmic localization that was attributed to a shared epitope between protein C23 and a 72 kD nuclear/nucleolar antigen. Reciprocal antibody cross blocking studies indicated that the ten MAbs identified nine distinct epitopes on protein C23. Interestingly, seven of the nine epitopes were shown by immunofluorescence and competitive ELISA studies to be species related. Immunostained patterns of exponentially growing HeLa cells suggest that protein C23 exists in vivo solely as a 110 kD peptide. However, protein C23 was subject to rapid degradation into a number of proteolytic fragments upon extraction or storage of isolated nucleoli. The failure to find protein C23 related peptides with molecular sizes less than 110 kD in exponentially growing cells and the lack of cytoplasmic localization of any of the ten MAbs suggests that protein C23 is not a prepro-protein processed in vivo to form ribosomal proteins as previously suggested (1). 相似文献