全文获取类型
收费全文 | 539篇 |
免费 | 35篇 |
出版年
2024年 | 1篇 |
2023年 | 6篇 |
2022年 | 11篇 |
2021年 | 31篇 |
2020年 | 14篇 |
2019年 | 16篇 |
2018年 | 16篇 |
2017年 | 11篇 |
2016年 | 25篇 |
2015年 | 19篇 |
2014年 | 34篇 |
2013年 | 35篇 |
2012年 | 51篇 |
2011年 | 47篇 |
2010年 | 27篇 |
2009年 | 35篇 |
2008年 | 29篇 |
2007年 | 30篇 |
2006年 | 23篇 |
2005年 | 20篇 |
2004年 | 19篇 |
2003年 | 17篇 |
2002年 | 18篇 |
2001年 | 6篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 5篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1978年 | 1篇 |
1972年 | 1篇 |
1969年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有574条查询结果,搜索用时 15 毫秒
91.
HIV-1 infections lead to a progressive depletion of CD4 cells culminating in AIDS. The coreceptor usage by HIV varies from CCR5 (R5) tropic early in infection to CXCR4 (X4) tropic in later infections. Although the coreceptor switch from R5 to X4 tropic HIV is well associated with progression to AIDS, the role of CCR5 in disease progression especially in patients infected exclusively with R5 isolates throughout the disease remains enigmatic. To better understand the role of CCR5 and R5 tropic HIV envelope in AIDS pathogenesis, we asked whether the levels of CCR5 and/or HIV Env-mediated fusion determine apoptosis of bystander cells. We generated CD4(+) T cell lines expressing varying levels of CCR5 on the cell surface to show that CCR5 expression levels correlate with bystander apoptosis induction. The mechanism of apoptosis involved caspase-3 activation and mitochondrial depolarization and was dependent on gp41 fusion activity as confirmed by fusion-restricted gp41 point mutants and use of the fusion inhibitor T20. Interestingly, lower levels of CCR5 were able to support virus replication in the absence of bystander apoptosis. Our findings suggest that R5 HIV-1-mediated bystander apoptosis is dependent on both CCR5 expression levels as well as fusogenic activity of the Env glycoprotein. 相似文献
92.
We have attempted to develop quantitative structure-toxicity relationships (QSTRs) to predict hydrophobicity (logP) as well as toxicity (pEC50 microm) of benzene derivatives using recently introduced Padmakar-Ivan (PI) index. The results have shown that both logP as well as pEC50 of benzene derivatives can be modelled excellently in multiparametric models in that the PI index and some indicator parameters are involved. The predictive ability of the models is discussed on the basis of the cross-validation method. The superiority of the PI index over several other topological indices is critically examined. 相似文献
93.
Anjali G. Hinch Nicolas Altemose Nudrat Noor Peter Donnelly Simon R. Myers 《PLoS genetics》2014,10(7)
The pseudoautosomal region (PAR) is a short region of homology between the mammalian X and Y chromosomes, which has undergone rapid evolution. A crossover in the PAR is essential for the proper disjunction of X and Y chromosomes in male meiosis, and PAR deletion results in male sterility. This leads the human PAR with the obligatory crossover, PAR1, to having an exceptionally high male crossover rate, which is 17-fold higher than the genome-wide average. However, the mechanism by which this obligatory crossover occurs remains unknown, as does the fine-scale positioning of crossovers across this region. Recent research in mice has suggested that crossovers in PAR may be mediated independently of the protein PRDM9, which localises virtually all crossovers in the autosomes. To investigate recombination in this region, we construct the most fine-scale genetic map containing directly observed crossovers to date using African-American pedigrees. We leverage recombination rates inferred from the breakdown of linkage disequilibrium in human populations and investigate the signatures of DNA evolution due to recombination. Further, we identify direct PRDM9 binding sites using ChIP-seq in human cells. Using these independent lines of evidence, we show that, in contrast with mouse, PRDM9 does localise peaks of recombination in the human PAR1. We find that recombination is a far more rapid and intense driver of sequence evolution in PAR1 than it is on the autosomes. We also show that PAR1 hotspot activities differ significantly among human populations. Finally, we find evidence that PAR1 hotspot positions have changed between human and chimpanzee, with no evidence of sharing among the hottest hotspots. We anticipate that the genetic maps built and validated in this work will aid research on this vital and fascinating region of the genome. 相似文献
94.
Khyati V. Pathak Anjali Bose Hareshkumar Keharia 《International journal of peptide research and therapeutics》2014,20(2):133-143
Microbes are known to interact and communicate with their neighbouring cells by releasing diverse types of low molecular weight diffusible metabolites. This paper describes the identification of iturins, fengycins and surfactins secreted by Bacillus tequilensis P15 isolated from sea coast of Jakhao, Kutch, India, using liquid chromatography coupled electron spray ionization tandem mass spectrometry. In methanol soluble fraction of acid precipitate harvested from cell free supernatant of B. tequilensis P15, 5 variants of iturins, 6 of fengycins and 39 surfactins could be identified. In particular, new surfactins with Ile/Leu at position 5 and Asp at position 6 in the peptide chain were discovered, which have not been previously reported. A novel class of novel surfactin consisting of Glu/methyl ester of Asp at position 5 in peptide chain was also identified. In addition, several linear forms of surfactins were also identified in the methanol soluble extracellular fraction of B. tequilensis P15. This is the first report on co-production of all the three classes of cyclic lipopeptides by a marine isolate B. tequilensis. 相似文献
95.
Steven A. Safren Katie B. Biello Laura Smeaton Matthew J. Mimiaga Ann Walawander Javier R. Lama Aadia Rana Mulinda Nyirenda Virginia M. Kayoyo Wadzanai Samaneka Anjali Joglekar David Celentano Ana Martinez Jocelyn E. Remmert Aspara Nair Umesh G. Lalloo Nagalingeswaran Kumarasamy James Hakim Thomas B. Campbell for the PEARLS Study Team 《PloS one》2014,9(8)
96.
97.
S. Sripriyalakshmi Pinkybel Jose Aswathy Ravindran C. H. Anjali 《Cell biochemistry and biophysics》2014,70(1):17-26
Engineered nanoparticles that can facilitate drug formulation and passively target tumours have been under extensive research in recent years. These successes have driven a new wave of significant innovation in the generation of advanced particles. The fate and transport of diagnostic nanoparticles would significantly depend on nonselective drug delivery, and hence the use of high drug dosage is implemented. In this perspective, nanocarrier-based drug targeting strategies can be used which improve the selective delivery of drugs to the site of action, i.e. drug targeting. Pharmaceutical industries majorly focus on reducing the toxicity and side effects of drugs but only recently it has been realised that carrier systems themselves may pose risks to the patient. Proteins are compatible with biological systems and they are biodegradable. They offer a multitude of moieties for modifications to tailor drug binding, imaging or targeting entities. Thus, protein nanoparticles provide outstanding contributions as a carrier for drug delivery systems. This review summarises recent progress in particle-based therapeutic delivery and discusses important concepts in particle design and biological barriers for developing the next generation of particles drug delivery systems. 相似文献
98.
Aeshna Nigam Khaled H. Almabruk Anjali Saxena Jongtae Yang Udita Mukherjee Hardeep Kaur Puneet Kohli Rashmi Kumari Priya Singh Lev N. Zakharov Yogendra Singh Taifo Mahmud Rup Lal 《The Journal of biological chemistry》2014,289(30):21142-21152
Rifamycin B, a product of Amycolatopsis mediterranei S699, is the precursor of clinically used antibiotics that are effective against tuberculosis, leprosy, and AIDS-related mycobacterial infections. However, prolonged usage of these antibiotics has resulted in the emergence of rifamycin-resistant strains of Mycobacterium tuberculosis. As part of our effort to generate better analogs of rifamycin, we substituted the acyltransferase domain of module 6 of rifamycin polyketide synthase with that of module 2 of rapamycin polyketide synthase. The resulting mutants (rifAT6::rapAT2) of A. mediterranei S699 produced new rifamycin analogs, 24-desmethylrifamycin B and 24-desmethylrifamycin SV, which contained modification in the polyketide backbone. 24-Desmethylrifamycin B was then converted to 24-desmethylrifamycin S, whose structure was confirmed by MS, NMR, and X-ray crystallography. Subsequently, 24-desmethylrifamycin S was converted to 24-desmethylrifampicin, which showed excellent antibacterial activity against several rifampicin-resistant M. tuberculosis strains. 相似文献
99.
Shailly Anand Sukanya Lal Utkarsh Sood Vipin Gupta Gauri Garg Dhingra Renu Solanki Jasvinder Kaur Roshan Kumar Anjali Saxena Ankita Dua Charu Tripathi Chandni Talwar Charu Dogra Rawat Harpreet Kaur Helianthous Verma Jaspreet Kaur Mansi Verma Mona Singh Princy Hira Nirjara Singhvi Nitish Kumar Mahato Om Prakash Jaya Malhotra Rup Lal Vipin Chandra Kalia 《Indian journal of microbiology》2021,61(4):397
100.
Kulkarni Anjali A. Thengane S.R. Krishnamurthy K.V. 《Plant Cell, Tissue and Organ Culture》2000,62(3):203-209
In vitro studies were initiated with Withania somnifera (L.) Dun. for rapid micropropagation of selected chemotypes using nodes, internodes, hypocotyls and embryo explants. Direct
regeneration of shoot buds was observed in MS basal medium supplemented with various concentrations of either benzyladenine
(BA) or thidiazouron (TDZ) depending on the explant. Nodal explants formed multiple shoots both from pre-existing and de novo buds on Murashige and Skoog's medium (MS) containing 0.1–5.0 mg l−1 BA and a ring of de novo shoot buds on MS medium containing 0.2 and 0.3 mg l−1 TDZ. Internodal explants formed shoot buds on MS with 1.0 and 5.0 mg l−1 BA while the hypocotyl explants gave rise to multiple shoots only on MS with 0.5 mg l−1 BA. Isolated embryos gave rise to many shoot buds on MS with 0.2 and 0.3 mg l−1 TDZ. The shoot buds elongated and rooted either on MS medium with 0.01 mg l−1 BA or on half strength MS medium lacking growth regulators, which depended upon the growth regulator used in the shoot bud
induction medium. Except for the embryo-derived plantlets, all other plantlets could be acclimatized with 100% success.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献