全文获取类型
收费全文 | 994篇 |
免费 | 56篇 |
专业分类
1050篇 |
出版年
2023年 | 7篇 |
2022年 | 9篇 |
2021年 | 18篇 |
2020年 | 14篇 |
2019年 | 22篇 |
2018年 | 24篇 |
2017年 | 29篇 |
2016年 | 24篇 |
2015年 | 29篇 |
2014年 | 46篇 |
2013年 | 51篇 |
2012年 | 75篇 |
2011年 | 80篇 |
2010年 | 51篇 |
2009年 | 43篇 |
2008年 | 50篇 |
2007年 | 52篇 |
2006年 | 45篇 |
2005年 | 53篇 |
2004年 | 38篇 |
2003年 | 31篇 |
2002年 | 34篇 |
2001年 | 23篇 |
2000年 | 17篇 |
1999年 | 16篇 |
1998年 | 12篇 |
1997年 | 6篇 |
1996年 | 9篇 |
1995年 | 5篇 |
1994年 | 3篇 |
1993年 | 12篇 |
1992年 | 13篇 |
1991年 | 8篇 |
1990年 | 8篇 |
1989年 | 10篇 |
1988年 | 6篇 |
1987年 | 12篇 |
1986年 | 2篇 |
1985年 | 4篇 |
1983年 | 3篇 |
1982年 | 9篇 |
1981年 | 10篇 |
1980年 | 6篇 |
1979年 | 12篇 |
1978年 | 6篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1964年 | 1篇 |
1944年 | 1篇 |
排序方式: 共有1050条查询结果,搜索用时 0 毫秒
991.
Background
It has been shown previously that it is possible to obtain growth of Plasmodium falciparum in human erythrocytes grafted in mice lacking adaptive immune responses by controlling, to a certain extent, innate defences with liposomes containing clodronate (clo-lip). However, the reproducibility of those models is limited, with only a proportion of animals supporting longstanding parasitemia, due to strong inflammation induced by P. falciparum. Optimisation of the model is much needed for the study of new anti-malarial drugs, drug combinations, and candidate vaccines.Materials/Methods
We investigated the possibility of improving previous models by employing the intravenous route (IV) for delivery of both human erythrocytes (huRBC) and P. falciparum, instead of the intraperitoneal route (IP), by testing various immunosuppressive drugs that might help to control innate mouse defences, and by exploring the potential benefits of using immunodeficient mice with additional genetic defects, such as those with IL-2Rγ deficiency (NSG mice).Results
We demonstrate here the role of aging, of inosine and of the IL-2 receptor γ mutation in controlling P. falciparum induced inflammation. IV delivery of huRBC and P. falciparum in clo-lip treated NSG mice led to successful infection in 100% of inoculated mice, rapid rise of parasitemia to high levels (up to 40%), long-lasting parasitemia, and consistent results from mouse-to-mouse. Characteristics were closer to human infection than in previous models, with evidence of synchronisation, partial sequestration, and receptivity to various P. falciparum strains without preliminary adaptation. However, results show that a major IL-12p70 inflammatory response remains prevalent.Conclusion
The combination of the NSG mouse, clodronate loaded liposomes, and IV delivery of huRBC has produced a reliable and more relevant model that better meets the needs of Malaria research. 相似文献992.
Singh Neetu Asthana R.K. Singh S.P. 《World journal of microbiology & biotechnology》2003,19(8):851-857
Exposure of the exopolysaccharide (EPS)-synthesizing cyanobacterium Nostoc spongiaeforme to Zn2+ (20 M) transformed the biomass into white debris. However, a few blue–green pin-heads emerged after 2 weeks in the same Zn2+-containing medium and formed less mucoid microcolonies (1–2 mm) relative to the protruding colonies (2–4 mm) of the parent strain on nutrient agar. One of such survivors (designated as Zn20) that was stable through 10 successive transfers in Zn2+-lacking medium has been adopted for further characterization. The parent strain retained almost 88% of the total EPS synthesized, the rest being released into the ambient medium, while for Zn20, the EPS retained approximated to 74%. Although the Zn2+-sensitivity of the mutant was comparable with that of the parent (LD50, 7 M), Zn2+ uptake was still 5-fold higher in the former (2 g mg–1 biomass dry wt., 20 M, external concentration). Also, both the strains showed insignificant difference in Zn2+-sorption onto their isolated EPS. The mutant was characterized by having higher cell carbohydrate content (642.8 g mg–1 dry wt.) than its parent (513.6 g). The X-ray diffraction pattern revealed Zn2+ deposition on EPS from the parent mainly as zinc hypophosphite monohydrate [Zn(H2PO2)2·H2O], whereas there was a lack of distinct peaks in similar samples from Zn20, thus confirming the amorphous nature. There was participation in Zn2+ binding of only COO–, N=O, NO2, SO2 groups in the parent while participation of P—O and C=O groups in mutant EPS was evident in IR spectra. The observations suggest that the mutant could be deployed to achieve sustained EPS synthesis, its release and metal sorption/desorption in repeated cycles. 相似文献
993.
994.
Amolkumar U. Solanke Manoj K. Sharma Akhilesh K. Tyagi Arun Kumar Sharma 《Molecular genetics and genomics : MGG》2009,282(2):153-164
Characterization of genes responsive to stress is important for efforts on improving stress tolerance of plants. To address
components involved in stress tolerance of tomato (Solanum lycopersicum), a stress-responsive gene family encoding A20/AN1 zinc finger proteins was characterized. In the present study, 13 members
of this gene family were cloned from tomato cultivar Pusa Ruby and named as Stress Associated Protein (SAP) genes. Out of 13 genes, 12 have been mapped on their respective chromosomes. Expression of these genes in response to cold,
heat, salt, desiccation, wounding, abscisic acid, oxidative and submergence stresses was analysed. All tomato SAP genes were found to be responsive to one or other type of environmental stress. The phylogenetic analysis of these genes,
along with their orthologs from Solanaceae species suggests the presence of a common set of SAP genes in the studied Solanaceae species. The present study characterizes a SAP gene family, which encodes A20/AN1 zinc finger containing proteins from tomato for the first time. Genes showing high expression
in response to a particular stress can be exploited for improving stress tolerance of tomato and other Solanaceae members.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
995.
Phani K. Patibandla Neetu Tyagi William L. Dean Suresh C. Tyagi Andrew M. Roberts David Lominadze 《Journal of cellular physiology》2009,221(1):195-203
We previously showed that an elevated content of fibrinogen (Fg) increased formation of filamentous actin and enhanced endothelial layer permeability. In the present work we tested the hypothesis that Fg binding to endothelial cells (ECs) alters expression of actin‐associated endothelial tight junction proteins (TJP). Rat cardiac microvascular ECs were grown in gold plated chambers of an electrical cell‐substrate impedance system, 8‐well chambered, or in 12‐well plates. Confluent ECs were treated with Fg (2 or 4 mg/ml), Fg (4 mg/ml) with mitogen‐activated protein kinase (MEK) kinase inhibitors (PD98059 or U0126), Fg (4 mg/ml) with anti‐ICAM‐1 antibody or BQ788 (endothelin type B receptor blocker), endothelin‐1, endothelin‐1 with BQ788, or medium alone for 24 h. Fg induced a dose‐dependent decrease in EC junction integrity as determined by transendothelial electrical resistance (TEER). Western blot analysis and RT‐PCR data showed that the higher dose of Fg decreased the contents of TJPs, occludin, zona occluden‐1 (ZO‐1), and zona occluden‐2 (ZO‐2) in ECs. Fg‐induced decreases in contents of the TJPs were blocked by PD98059, U0126, or anti‐ICAM‐1 antibody. While BQ788 inhibited endothelin‐1‐induced decrease in TEER, it did not affect Fg‐induced decrease in TEER. These data suggest that Fg increases EC layer permeability via the MEK kinase signaling pathway by affecting occludin, ZO‐1, and ZO‐2, TJPs, which are bound to actin filaments. Therefore, increased binding of Fg to its major EC receptor, ICAM‐1, during cardiovascular diseases may increase microvascular permeability by altering the content and possibly subcellular localization of endothelial TJPs. J. Cell. Physiol. 221: 195–203, 2009. © 2009 Wiley‐Liss, Inc 相似文献
996.
V. Ravi Jitendra P. Khurana Akhilesh K. Tyagi Paramjit Khurana 《Tree Genetics & Genomes》2006,3(1):49-59
The complete nucleotide sequence of mulberry (Morus indica cv. K2) chloroplast genome (158,484 bp) has been determined using a combination of long PCR and shotgun-based approaches. This is the third angiosperm tree species whose plastome sequence has been completely deciphered. The circular double-stranded molecule comprises of two identical inverted repeats (25,678 bp each) separating a large and a small single-copy region of 87,386 bp and 19,742 bp, respectively. A total of 83 protein-coding genes including five genes duplicated in the inverted repeat regions, eight ribosomal RNA genes and 37 tRNA genes (30 gene species) representing 20 amino acids, were assigned on the basis of homology to predicted genes from other chloroplast genomes. The mulberry plastome lacks the genes infA, sprA, and rpl21 and contains two pseudogenes ycf15 and ycf68. Comparative analysis, based on sequence similarity, both at the gene and genome level, indicates Morus to be closer to Cucumis and Lotus, phylogenetically. However, at genome level, inclusion of non-coding regions brings it closer to Eucalyptus, followed by Cucumis. This may reflect differential selection pressure operating on the genic and intergenic regions of the chloroplast genome.Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.Communicated by Y. Tsumura 相似文献
997.
Ruoqi Peng Sriram Sridhar Gaurav Tyagi Jonathan E. Phillips Rosario Garrido Paul Harris Lisa Burns Lorena Renteria John Woods Leena Chen John Allard Palanikumar Ravindran Hans Bitter Zhenmin Liang Cory M. Hogaboam Chris Kitson David C. Budd Jay S. Fine Carla MT. Bauer Christopher S. Stevenson 《PloS one》2013,8(4)
The preclinical model of bleomycin-induced lung fibrosis, used to investigate mechanisms related to idiopathic pulmonary fibrosis (IPF), has incorrectly predicted efficacy for several candidate compounds suggesting that it may be of limited value. As an attempt to improve the predictive nature of this model, integrative bioinformatic approaches were used to compare molecular alterations in the lungs of bleomycin-treated mice and patients with IPF. Using gene set enrichment analysis we show for the first time that genes differentially expressed during the fibrotic phase of the single challenge bleomycin model were significantly enriched in the expression profiles of IPF patients. The genes that contributed most to the enrichment were largely involved in mitosis, growth factor, and matrix signaling. Interestingly, these same mitotic processes were increased in the expression profiles of fibroblasts isolated from rapidly progressing, but not slowly progressing, IPF patients relative to control subjects. The data also indicated that TGFβ was not the sole mediator responsible for the changes observed in this model since the ALK-5 inhibitor SB525334 effectively attenuated some but not all of the fibrosis associated with this model. Although some would suggest that repetitive bleomycin injuries may more effectively model IPF-like changes, our data do not support this conclusion. Together, these data highlight that a single bleomycin instillation effectively replicates several of the specific pathogenic molecular changes associated with IPF, and may be best used as a model for patients with active disease. 相似文献
998.
999.
1000.