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821.
Xianjin Zhu Lianbo Xiao Rongfen Huo Jie Zhang Jinpiao Lin Jun Xie Songtao Sun Yong He Yue Sun Zhou Zhou Baihua Shen Ningli Li 《Arthritis research & therapy》2013,15(6):R187
Introduction
It is well known that neutrophils play very important roles in the development of rheumatoid arthritis (RA) and interleukin (IL)-8 is a critical chemokine in promoting neutrophil migration. We previously showed that increased production of Cyr61 by fibroblast-like synoviocytes (FLS) in RA promotes FLS proliferation and Th17 cell differentiation, thus Cyr61 is a pro-inflammatory factor in RA pathogenesis. In this study, we explored the role of Cyr61 in neutrophil migration to the joints of RA patients.Methods
RA FLS were treated with Cyr61 and IL-8 expression was analyzed by real-time PCR and ELISA. The migration of neutrophils recruited by the culture supernatants was determined by the use of a chemotaxis assay. Mice with collagen-induced arthritis (CIA) were treated with anti-Cyr61 monoclonal antibodies (mAb), or IgG1 as a control. Arthritis severity was determined by visual examination of the paws and joint destruction was determined by hematoxylin-eosin (H&E) staining. Signal transduction pathways in Cyr61-induced IL-8 production were investigated by real-time PCR, western blotting, confocal microscopy, luciferase reporter assay or chromatin immunoprecipitation (ChIP) assay.Results
We found that Cyr61 induced IL-8 production by RA FLS in an IL-1β and TNF-α independent pathway. Moreover, we identified that Cyr61-induced IL-8-mediated neutrophil migration in vitro. Using a CIA animal model, we found that treatment with anti-Cyr61 mAb led to a reduction in MIP-2 (a counterpart of human IL-8) expression and decrease in neutrophil infiltration, which is consistent with an attenuation of inflammation in vivo. Mechanistically, we showed that Cyr61 induced IL-8 production in FLS via AKT, JNK and ERK1/2-dependent AP-1, C/EBPβ and NF-κB signaling pathways.Conclusions
Our results here reveal a novel role of Cyr61 in the pathogenesis of RA. It promotes neutrophil infiltration via up-regulation of IL-8 production in FLS. Taken together with our previous work, this study provides further evidence that Cyr61 plays a key role in the vicious cycle formed by the interaction between infiltrating neutrophils, proliferated FLS and activated Th17 cells in the development of RA. 相似文献822.
A novel chemiluminescence (CL) method was developed for the determination of cefazolin sodium based on the CL reaction between the [Cu(HIO6)2]5‐Cu(III) complex and luminol in alkaline solution. Results showed that CL emission of Cu(III) complex–luminol in alkaline medium was significantly different from that in acidic medium. A possible mechanism of the enhanced effect of cefazolin on CL emission of the [Cu(HIO6)2]5‐‐ luminol system was proposed. The effect of the reaction conditions on CL emissions was examined. Under optimized conditions, a good linear relationship was obtained between CL intensity and concentrations of cefazolin sodium in the range of 2.0 x 10‐8 to 2.0 x 10‐6 g/mL with a correlation coefficient of R2 = 0.9978. The limit of detection was 4.58 x 10‐9 g/mL. The proposed method was applied for the determination of cefazolin sodium in real samples with recoveries of 82.0‐109% with an RSD of 0.7‐2.1%. The proposed method was successfully used for the determination of cefazolin sodium in injectable powder preparations and human urine with satisfactory results. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
823.
Chun Wu Ke‐Yong Wang Xin Guo Masanori Sato Michitaka Ozaki Shyohei Shimajiri Yoshihiro Ohmiya Yasuyuki Sasaguri 《Luminescence》2013,28(1):38-43
We demonstrate a novel rapid direct detection method for immunohistochemistry, using a bioluminescent probe. An anti‐CEA antibody‐fused far‐red bioluminescent protein can monitor the accumulation of this type of probe in tumour tissues. The bimodal spectrum (λmax = 460 and 675 nm) of this bioluminescent probe is extremely stable under different conditions of pH and ion concentration. The sensitivity of our bioluminescent labelling was at the same level of enzymatic labelling, e.g. peroxidase, as an indirect system. Our novel technique is simple and can shorten the pretreatment time of paraffin sections to around 30 min. The utility of our bioluminescent labelling covers all imaging in vitro, in vivo and ex vivo, suggesting that our antibody‐fused bioluminescent probe has the potential to detect tumour antigens with a high sensitivity in routine immune histological examinations. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
824.
Abstract 3′-Thio-3′-deoxyribonucleosides (U and C) have been synthesized via Vorbruggen-type glycosylation with 3-S-benzoyl-5-O-toluoyl-1,2-O-diacetylfuranose, which was obtained from 1,2-O-isopropylidene-5-O-toluoyl-3-O-trifluoromethanesulfonyl-α-D-xylofuranose. 3′-Thio-3′-deoxyuridine has been converted to its phosphoramidite. 相似文献
825.
Shiv Kumar C. W. Fuller S. Nampalli M. Khot I. Livshin L. Sun 《Nucleosides, nucleotides & nucleic acids》2013,32(4-5):1101-1103
Abstract The use of Cyanine dye (CyTM 5 and Cy5.5) labeled dideoxy terminators with Thermo SequenaseTM DNA polymerase in DNA sequencing provides uniform band intensity, improved sequence read-length, and accuracy. It also greatly improves the ability to detect single base heterozygotes with dye-terminator sequencing method. 相似文献
826.
Sudhir Agrawal Zhiwei Jiang Qiuyan Zhao Denise Shaw Daisy Sun Carl Saxinger 《Nucleosides, nucleotides & nucleic acids》2013,32(7-9):927-936
Abstract Antisense oligonucleotides are being studied as novel therapeutic agents. To further improve the properties of antisense oligonucleotides, we have synthesized phosphorothioate oligonucleotides containing methylphosphonate linkages at the 5′-end, the 3′-end, or in the center, and have evaluated the impact of these linkages on the biophysical properties, biological properties, and some of the safety parameters. 相似文献
827.
I. Basnak M. Sun T. A. Hamor F. Focher A. Verri S. Spadari 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):187-206
Abstract The synthesis and X-ray crystal structures of a series of 5-substituted-6-aza-2′-deoxyuridines is reported. These nucleoside analogues inhibit the phosphorylation of thymidine by HSV-1 TK but have no effect on the corresponding human enzyme. Detailed examination of one analogue proves it to be a competitive inhibitor of thymidine with a Ki of 0.34 μM and is a very poor substrate. The analogues are not substrates for the enzyme and also do not inhibit the degradation of thymidine by thymidine phosphorylase. Molecular modelling showed that the inhibitors fit well in the active site of HSV-1 TK, provided the conformation of the sugar moiety is the same for thymidine in the complex. 相似文献
828.
Victor E. Marquez Lak S. Jeong Marc C. Nicklaus Cliff George 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):555-558
Abstract The efficient DAST fluorination of deoxy-4′-thiopyrimidine nucleosides is reported. The cytidine analogue 3b was marginally effective against HIV. 相似文献
829.
Frank Seela Anup M. Jawalekar Lijuan Sun Peter Leonard 《Nucleosides, nucleotides & nucleic acids》2013,32(10-12):1485-1505
The synthesis of the 2′-deoxyadenosine analogues 1b, 2b, and 3c modified at the 7- and/or 2-position is described. The effect of 7-chloro and 2-methylthio groups on the duplex stability is evaluated. For that, the nucleosides 1b, 2b, and 3c were converted to the corresponding phosphoramidites 15, 19, and 22, which were employed in the solid-phase oligonucleotide synthesis. In oligonucleotide duplexes, compound 1b forms stable base pairs with dT, of which the separated 1b- dT base pairs contribute stronger than that of the consecutive base pairs. Compound 2b shows universal base pairing properties while its N8 isomer 3c forms duplexes with lower stability. 相似文献
830.
Sanhao Ji Yong Ju Hua Fu Yufen Zhao Tommy Johansson Jacek Stawinski 《Nucleosides, nucleotides & nucleic acids》2013,32(7):771-784
2-,3-,4-Pyridylphosphonates and their phosphonothioate congeners were analyzed by electrospray ionization multistage tandem mass spectrometry (ESI-MSn). It was found that the fragmentation pathways of these compounds were not influenced to any detectable extent by the stereochemistry at the phosphorus centers but were sensitive to the position of a nitrogen atom in the pyridine ring of these compounds. Possible mechanisms for fragmentations of the investigated compounds are discussed in detail. 相似文献