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1.
A polyurethane-foam enlarged reconstruction was made from serial sections of a portion of young adult human lung parenchyman. Study of the progeny of a terminal bronchiole disclosed three generations of respiratory bronchioles and an irregular branching pattern of eight generations of alveolar ducts. Sacs and alveoli arose from the lateral and distal aspects of all generations of ducts. There were an average of 3.5 alveoli per sac. Considering the terminal bronchiole as the first generation branch of the acinus, over 60 per cent of the alveoli counted and predicted were members of the 10-12th generations. The acinus contained one terminal bronchiole and approximately 14 respiratory bronchioles, 1,200-1,500 ducts, 2,500-4,500 sacs, and 14,000-20,000 alveoli. 相似文献
2.
CpG-induced tyrosine phosphorylation occurs via a TLR9-independent mechanism and is required for cytokine secretion 总被引:2,自引:0,他引:2 下载免费PDF全文
Sanjuan MA Rao N Lai KT Gu Y Sun S Fuchs A Fung-Leung WP Colonna M Karlsson L 《The Journal of cell biology》2006,172(7):1057-1068
Toll-like receptors (TLRs) recognize molecular patterns preferentially expressed by pathogens. In endosomes, TLR9 is activated by unmethylated bacterial DNA, resulting in proinflammatory cytokine secretion via the adaptor protein MyD88. We demonstrate that CpG oligonucleotides activate a TLR9-independent pathway initiated by two Src family kinases, Hck and Lyn, which trigger a tyrosine phosphorylation–mediated signaling cascade. This cascade induces actin cytoskeleton reorganization, resulting in cell spreading, adhesion, and motility. CpG-induced actin polymerization originates at the plasma membrane, rather than in endosomes. Chloroquine, an inhibitor of CpG-triggered cytokine secretion, blocked TLR9/MyD88-dependent cytokine secretion as expected but failed to inhibit CpG-induced Src family kinase activation and its dependent cellular responses. Knock down of Src family kinase expression or the use of specific kinase inhibitors blocked MyD88-dependent signaling and cytokine secretion, providing evidence that tyrosine phosphorylation is both CpG induced and an upstream requirement for the engagement of TLR9. The Src family pathway intersects the TLR9–MyD88 pathway by promoting the tyrosine phosphorylation of TLR9 and the recruitment of Syk to this receptor. 相似文献
3.
Navin Kumar Verma Kieran Crosbie-Staunton Amro Satti Shane Gallagher Katie B Ryan Timothy Doody Colm McAtamney Ronan MacLoughlin Paul Galvin Conor S Burke Yuri Volkov Yurii K Gun’ko 《Journal of nanobiotechnology》2013,11(1):1-12
Background
Aerosolized therapeutics hold great potential for effective treatment of various diseases including lung cancer. In this context, there is an urgent need to develop novel nanocarriers suitable for drug delivery by nebulization. To address this need, we synthesized and characterized a biocompatible drug delivery vehicle following surface coating of Fe3O4 magnetic nanoparticles (MNPs) with a polymer poly(lactic-co-glycolic acid) (PLGA). The polymeric shell of these engineered nanoparticles was loaded with a potential anti-cancer drug quercetin and their suitability for targeting lung cancer cells via nebulization was evaluated.Results
Average particle size of the developed MNPs and PLGA-MNPs as measured by electron microscopy was 9.6 and 53.2 nm, whereas their hydrodynamic swelling as determined using dynamic light scattering was 54.3 nm and 293.4 nm respectively. Utilizing a series of standardized biological tests incorporating a cell-based automated image acquisition and analysis procedure in combination with real-time impedance sensing, we confirmed that the developed MNP-based nanocarrier system was biocompatible, as no cytotoxicity was observed when up to 100 μg/ml PLGA-MNP was applied to the cultured human lung epithelial cells. Moreover, the PLGA-MNP preparation was well-tolerated in vivo in mice when applied intranasally as measured by glutathione and IL-6 secretion assays after 1, 4, or 7 days post-treatment. To imitate aerosol formation for drug delivery to the lungs, we applied quercitin loaded PLGA-MNPs to the human lung carcinoma cell line A549 following a single round of nebulization. The drug-loaded PLGA-MNPs significantly reduced the number of viable A549 cells, which was comparable when applied either by nebulization or by direct pipetting.Conclusion
We have developed a magnetic core-shell nanoparticle-based nanocarrier system and evaluated the feasibility of its drug delivery capability via aerosol administration. This study has implications for targeted delivery of therapeutics and poorly soluble medicinal compounds via inhalation route. 相似文献4.
Ken Chen Nicholas E Navin Yong Wang Heather K Schmidt John W Wallis Beifang Niu Xian Fan Hao Zhao Michael D McLellan Katherine A Hoadley Elaine R Mardis Timothy J Ley Charles M Perou Richard K Wilson Li Ding 《Genome biology》2013,14(8):R87
Producing gene fusions through genomic structural rearrangements is a major mechanism for tumor evolution. Therefore, accurately detecting gene fusions and the originating rearrangements is of great importance for personalized cancer diagnosis and targeted therapy. We present a tool, BreakTrans, that systematically maps predicted gene fusions to structural rearrangements. Thus, BreakTrans not only validates both types of predictions, but also provides mechanistic interpretations. BreakTrans effectively validates known fusions and discovers novel events in a breast cancer cell line. Applying BreakTrans to 43 breast cancer samples in The Cancer Genome Atlas identifies 90 genomically validated gene fusions. BreakTrans is available at http://bioinformatics.mdanderson.org/main/BreakTrans 相似文献
5.
Sheikh M. Talha Jukka Hyt?nen Adam Westhorpe Sushil Kumar Navin Khanna Kim Pettersson 《PloS one》2013,8(12)
Treponema pallidum subspecies pallidum (Tp) is the causative agent of syphilis which mainly spreads through sexual contact, blood transfusion and perinatal route. In order to curtail the spread of the infection and to clinically manage the disease, timely, accurate and reliable diagnosis is very important. We have developed an immunoassay for the detection of treponemal antibodies in human serum or plasma samples. In vivo biotinylated and non-biotinylated versions of the recombinant antigen were designed by the fusion of three Tp-specific antigens namely Tp15, Tp17 and Tp47. These fusion antigens were expressed in E. coli and purified using single-step metal affinity chromatography. Biotinylated fusion antigen immobilized on streptavidin coated plate was used to capture the treponemal antibodies and the non-biotinylated antigen coated on europium nanoparticles was used as tracer. Assays with two different incubation times of 10 min and 1 h were developed, and following the incubation the europium fluorescence was measured using time-resolved fluorometry. The developed time-resolved fluorometric (TRF) immunoassays were evaluated with in-house and commercial serum/plasma sample panels. For well-established treponemal antibodies positive or negative samples, the sensitivity of TRF immunoassay with 10 min incubation time was 97.4%, and of TRF immunoassay with 1 h incubation time was 98.7%, and the specificities of both the TRF immunoassays were 99.2%. For the samples with discordant results with the reference assays, both the TRF immunoassays showed better specificity than the Enzygnost syphilis enzyme immunoassay as a screening test. The two different incubation times did not have any significant effect on the signal to cutoff (S/Co) ratios obtained with the two immunoassays (p = 0.06). Our results indicate that the developed immunoassay with a short incubation time of 10 min has the potential to be used in clinical laboratories and in blood-bank settings as a screening test for treponemal antibodies. 相似文献
6.
A novel 4-nitrotoluene-degrading bacterial strain was isolated from pesticides contaminated effluent-sediment and identified as Rhodococcus pyridinivorans NT2 based on morphological and biochemical properties and 16S rDNA sequencing. The strain NT2 degraded 4-NT (400 mg l?1) with rapid growth at the end of 120 h, reduced surface tension of the media from 71 to 29 mN m?1 and produced glycolipidic biosurfactants (45 mg l?1). The biosurfactant was purified and characterized as trehalose lipids. The biosurfactant was stable in high salinity (10 % w/v NaCl), elevated temperatures (120 °C for 15 min) and a wide pH range (2.0–10.0). The noticeable changes during biodegradation were decreased hydrophobicity; an increase in degree of fatty acid saturation, saturated/unsaturated ratio and cyclopropane fatty acid. Biodegradation of 4-NT was accompanied by the accumulation of ammonium (NH4 +) and negligible amount of nitrite ion (NO2 ?). Product stoichiometry showed a carbon (C) and nitrogen (N) mass balance of 37 and 35 %, respectively. Biodegradation of 4-NT proceeded by oxidation at the methyl group to form 4-nitrobenzoate, followed by reduction and hydrolytic deamination yielding protocatechuate, which was metabolized through β-ketoadipate pathway. In vitro and in vivo acute toxicity assays in adult rat (Rattus norvegicus) showed sequential detoxification and the order of toxicity was 4-NT >4-nitrobenzyl alcohol >4-nitrobenzaldehyde >4-nitrobenzoate >> protocatechuate. Taken together, the strain NT2 could be used as a potential bioaugmentation candidate for the bioremediation of contaminated sites. 相似文献
7.
Chandrasekaran Uma Burkhoff Daniel Ishikawa Kiyotake Swain Lija Sunagawa Kenji Mller Jacob Santos-Gallego Carlos Annamalai Shiva Udelson James Westenfeld Ralf Kapur Navin Qiao Xiaoying Wiora Julian Schfer Andreas Bernhardt Alexander Kochar Ajar Kloner Robert Faraz Haroon 《BMC cardiovascular disorders》2019,19(2):1-17
8.
Lijuan Sun Sanjay Verma Navin Michael Siew Pang Chan Jianhua Yan Suresh Anand Sadananthan Stefan G. Camps Hui Jen Goh Priya Govindharajulu John Totman David Townsend Julian Pak‐Nam Goh Lei Sun Bernhard Otto Boehm Su Chi Lim Siew Kwan Sze Christiani Jeyakumar Henry Houchun Harry Hu S. Sendhil Velan Melvin Khee‐Shing Leow 《Obesity (Silver Spring, Md.)》2019,27(9):1434-1442
9.
Suresh Anand Sadananthan Mya Thway Tint Navin Michael Izzuddin M. Aris See Ling Loy Kuan Jin Lee Lynette Pei‐Chi Shek Fabian Kok Peng Yap Kok Hian Tan Keith M. Godfrey Melvin Khee‐Shing Leow Yung Seng Lee Michael S. Kramer Peter D. Gluckman Yap Seng Chong Neerja Karnani Christiani Jeyakumar Henry Marielle Valerie Fortier S. Sendhil Velan 《Obesity (Silver Spring, Md.)》2019,27(3):470-478
10.
We have isolated an amphioxus T-box gene that is orthologous to the two vertebrate genes, Tbx1 and Tbx10, and examined its expression pattern during embryonic and early larval development. AmphiTbx1/10 is first expressed in branchial arch endoderm and mesoderm of developing neurulae, and in a bilateral, segmented pattern in the ventral half of newly formed somites. Branchial expression is restricted to the first three branchial arches, and disappears completely by 4 days post fertilization. Ventral somitic expression is restricted to the first 10–12 somites, and is not observed in early larvae except in the most ventral mesoderm of the first three branchial arches. No expression can be detected by 4 days post fertilization. Integrating functional, phylogenetic and expression data from amphioxus and a variety of vertebrate model organisms, we have reconstructed the early evolutionary history of the Tbx1/10 subfamily of genes within the chordate lineage. We conclude that Tbx1/10-mediated branchial arch endoderm and mesoderm patterning functions predated the origin of neural crest, and that ventral somite specification functions predated the origin of vertebrate sclerotome, but that Tbx1 was later co-opted during the evolution of developmental programs regulating branchial neural crest and sclerotome migration.Edited by M. Akam 相似文献