全文获取类型
收费全文 | 2705篇 |
免费 | 270篇 |
国内免费 | 5篇 |
出版年
2023年 | 19篇 |
2022年 | 11篇 |
2021年 | 56篇 |
2020年 | 23篇 |
2019年 | 36篇 |
2018年 | 54篇 |
2017年 | 40篇 |
2016年 | 57篇 |
2015年 | 122篇 |
2014年 | 125篇 |
2013年 | 173篇 |
2012年 | 229篇 |
2011年 | 215篇 |
2010年 | 114篇 |
2009年 | 99篇 |
2008年 | 161篇 |
2007年 | 145篇 |
2006年 | 154篇 |
2005年 | 106篇 |
2004年 | 102篇 |
2003年 | 87篇 |
2002年 | 89篇 |
2001年 | 87篇 |
2000年 | 74篇 |
1999年 | 56篇 |
1998年 | 18篇 |
1997年 | 19篇 |
1996年 | 25篇 |
1995年 | 29篇 |
1994年 | 22篇 |
1993年 | 11篇 |
1992年 | 35篇 |
1991年 | 18篇 |
1990年 | 33篇 |
1989年 | 35篇 |
1988年 | 28篇 |
1987年 | 19篇 |
1986年 | 22篇 |
1985年 | 29篇 |
1984年 | 14篇 |
1983年 | 17篇 |
1982年 | 12篇 |
1981年 | 10篇 |
1980年 | 17篇 |
1979年 | 24篇 |
1977年 | 10篇 |
1975年 | 14篇 |
1973年 | 10篇 |
1970年 | 10篇 |
1969年 | 12篇 |
排序方式: 共有2980条查询结果,搜索用时 15 毫秒
71.
72.
F. A. Azevedo F. A. A. Mourão Filho B. M. J. Mendes W. A. B. Almeida E. H. Schinor R. Pio J. M. Barbosa S Guidetti-Gonzalez H. Carrer E. Lam 《Plant Molecular Biology Reporter》2006,24(2):185-196
Transgenic plants expressing the bacterio-opsin (bO) gene can spontaneously activate programmed cell death (ped) and may enhance broad-spectrum pathogen resistance by activating
an intrinsic defense pathway in plant species such as tobacco and potato. In this work, we produced transgenic Rangpur lime
plants with thebO gene, viaAgrobacterium tumefaciens-mediated transformation, and evaluated these plants forPhytophthora nicotianae resistance. Two transgenic lines were successfully regenerated and transformation was confirmed by GUS activity assay, PCR
analysis, Southern, Northern and Western blot analyses, in addition to detecting the expressed bO protein by an immunological
approach. Evaluation forPhytophthora nicotianae resistance was carried out by plant inoculations with the pathogen and quantification of the affected area. One of the two
transgenic lines showed greater tolerance to the fungal pathogen as compared to the control, with significantly smaller stem
lesions after pathogen challenge. This increase in pathogen tolerance is correlated with a significantly higher level of transgene
expression in this line when compared with the other transgenic line. This is the first report of the introduction of a potentially
important gene into Rangpur lime to provide novel pathogen tolerance. 相似文献
73.
Alex R. Hastie Lingli Dong Alexis Smith Jeff Finklestein Ernest T. Lam Naxin Huo Han Cao Pui-Yan Kwok Karin R. Deal Jan Dvorak Ming-Cheng Luo Yong Gu Ming Xiao 《PloS one》2013,8(2)
Next-generation sequencing (NGS) technologies have enabled high-throughput and low-cost generation of sequence data; however, de novo genome assembly remains a great challenge, particularly for large genomes. NGS short reads are often insufficient to create large contigs that span repeat sequences and to facilitate unambiguous assembly. Plant genomes are notorious for containing high quantities of repetitive elements, which combined with huge genome sizes, makes accurate assembly of these large and complex genomes intractable thus far. Using two-color genome mapping of tiling bacterial artificial chromosomes (BAC) clones on nanochannel arrays, we completed high-confidence assembly of a 2.1-Mb, highly repetitive region in the large and complex genome of Aegilops tauschii, the D-genome donor of hexaploid wheat (Triticum aestivum). Genome mapping is based on direct visualization of sequence motifs on single DNA molecules hundreds of kilobases in length. With the genome map as a scaffold, we anchored unplaced sequence contigs, validated the initial draft assembly, and resolved instances of misassembly, some involving contigs <2 kb long, to dramatically improve the assembly from 75% to 95% complete. 相似文献
74.
Ramzi Fattouh Cong-Hui Guo Grace Y. Lam Melanie G. Gareau Bo-Yee Ngan Michael Glogauer Aleixo M. Muise John H. Brumell 《PloS one》2013,8(4)
Recent genetic-based studies have implicated a number of immune-related genes in the pathogenesis of inflammatory bowel disease (IBD). Our recent genetic studies showed that RAC2 is associated with human IBD; however, its role in disease pathogenesis is unclear. Given Rac2’s importance in various fundamental immune cell processes, we investigated whether a defect in Rac2 may impair host immune responses in the intestine and promote disease in the context of an infection-based (Citrobacter rodentium) model of colitis. In response to infection, Rac2−/− mice showed i) worsened clinical symptoms (days 13–18), ii) increased crypt hyperplasia at days 11 and 22 (a time when crypt hyperplasia was largely resolved in wild-type mice; WT), and iii) marked mononuclear cell infiltration characterized by higher numbers of T (CD3+) cells (day 22), compared to WT-infected mice. Moreover, splenocytes harvested from infected Rac2−/− mice and stimulated in vitro with C. rodentium lysate produced considerably higher levels of interferon-γ and interleukin-17A. The augmented responses observed in Rac2−/− mice did not appear to stem from Rac2’s role in NADPH oxidase-driven reactive oxygen species production as no differences in crypt hyperplasia, nor inflammation, were observed in infected NOX2−/− mice compared to WT. Collectively, our findings demonstrate that Rac2−/− mice develop more severe disease when subjected to a C. rodentium-induced model of infectious colitis, and suggest that impaired Rac2 function may promote the development of IBD in humans. 相似文献
75.
Abstract An efficient alternative which makes use of the reliable 3J1′2′. value to derive the endocyclic torsion angle constraints is proposed in this study. Based on the information embedded in the two plots, (i) the vicinal proton-proton J-couplings, 3J1′2′., 3J1′2″., 3J2′3′., 3J2”3′ and 3J3′4′ against the pseudorotation phase angle, and (ii) 3J1′2″, 3J2′3′., 3J2″3′ and 3J3′4′ against 3J1′2′; using the calculated J-couplings obtained for a range of sugar geometries of deoxyribose ring in nucleosides and nucleotides encountered along the pseudorotation itinerary [J. van Wijk, B.D. Huckriede, J.H. Ippel and C. Altona, Methods Enzymol. 211, 286–306 (1992)], it is suggested that the vicinal 3J1′2′ possesses structural information other than the vicinal torsion angle φ1′2′. This study is divided into two parts. In Part I, a correlation diagram between the endocyclic torsion angles vi (i=0,1,2,3,4) and the restrained vicinal torsion angle φ1′2′ is obtained through the use of the J-coupling restrained molecular mechanics (JrMM) protocol. The established φ1′2′.-vi correlation shows vi can be deduced from the reliable 3J1′2′. value and it forms the basis for developing an alternative protocol to derive endocyclic torsion angle constraints. In Part II of this series, extensive testing demonstrating the validity of the JrMM protocol to derive Vi for defining the sugar geometry of solution DNA molecules is presented. 相似文献
76.
PJ Cai X Xiao YR He WW Li GL Zang GP Sheng M Hon-Wah Lam L Yu HQ Yu 《Biosensors & bioelectronics》2013,39(1):306-310
The enhanced electricity generation in a biocathode bio-electrochemical system (BES) with Microcystis aeruginosa IPP as the cathodic microorganism under illumination is investigated. The results show that this cyanobacterium is able to act as a potential cathodic microorganism under illumination. In addition, M. aeruginosa IPP is found to produce reactive oxygen species (ROS) in its growth in the BES. ROS, as more competitive electron acceptors than oxygen, are utilized prior to oxygen. The BES current is substantially reduced when the ROS production is inhibited by mannitol, indicating that the ROS secreted by the cyanobacterium play an important role in the electricity generation of such a biocathode BES. This work demonstrates that the ROS released by cyanobacteria benefit for an enhanced electricity generation of BES. 相似文献
77.
Zhe Nie Victoria Feher Srinivasa Natala Christopher McBride Andre Kiryanov Benjamin Jones Betty Lam Yan Liu Stephen Kaldor Jeffrey Stafford Kouki Hikami Noriko Uchiyama Tomohiro Kawamoto Yuichi Hikichi Shin-ichi Matsumoto Nobuyuki Amano Lilly Zhang David Hosfield Takashi Ichikawa 《Bioorganic & medicinal chemistry letters》2013,23(12):3662-3666
Using structure-based drug design, we identified and optimized a novel series of pyrimidodiazepinone PLK1 inhibitors resulting in the selection of the development candidate TAK-960. TAK-960 is currently undergoing Phase I evaluation in adult patients with advanced solid malignancies. 相似文献
78.
Zhinxin Zhao Roberto Gambari Kenneth Ka-Ho Lee Stanton Hon-Lung Kok Raymond Siu-Ming Wong Fung-Yi Lau Johnny Cheuk-On Tang Kim-Hung Lam Chor-Hing Cheng Desmond Kwok Po Hau Chung-Hin Chui Wai-Yeung Wong Wai-Kwok Wong 《Bioorganic & medicinal chemistry letters》2013,23(8):2373-2376
We explore the possible cellular cytotoxic activity of an amphiphilic silicon(IV) phthalocyanine with axially ligated rhodamine B under ambient light experimental environment as well as its in vivo antitumour potential using Hep3B hepatoma cell model. After loading into the Hep3B hepatoma cells, induction of cellular cytotoxicity and cell cycle arrest were detected. Strong growth inhibition of tumour xenograft together with significant tumour necrosis and limited toxicological effects exerted on the nude mice could be identified. 相似文献
79.
Shuo Wang Hidenori Tanaka Ole Hindsgaul Joseph S. Lam Inka Brockhausen 《Bioorganic & medicinal chemistry letters》2013,23(12):3491-3495
Gram negative bacteria have lipopolysaccharides (LPS) that are critical for their survival. LPS molecules are composed of antigenic exopolysaccharide chains (O antigens). We are interested in discovering the enzymes involved in the biosynthesis of O antigens in Pseudomonas aeruginosa. The common polysaccharide antigen contains α-linked d-rhamnose residues. We have now synthesized GDP-d-rhamnose by a convenient synthesis in aqueous solution, and have shown that it can be used without extensive purification as the donor substrate for d-rhamnosyltransferase (WbpZ) from the P. aeruginosa strain PAO1. The availability of this nucleotide sugar preparation allows for characterization of d-rhamnosyltransferases. 相似文献
80.
Leslie W. Tari Michael Trzoss Daniel C. Bensen Xiaoming Li Zhiyong Chen Thanh Lam Junhu Zhang Christopher J. Creighton Mark L. Cunningham Bryan Kwan Mark Stidham Karen J. Shaw Felice C. Lightstone Sergio E. Wong Toan B. Nguyen Jay Nix John Finn 《Bioorganic & medicinal chemistry letters》2013,23(5):1529-1536
The bacterial topoisomerases DNA gyrase (GyrB) and topoisomerase IV (ParE) are essential enzymes that control the topological state of DNA during replication. The high degree of conservation in the ATP-binding pockets of these enzymes make them appealing targets for broad-spectrum inhibitor development. A pyrrolopyrimidine scaffold was identified from a pharmacophore-based fragment screen with optimization potential. Structural characterization of inhibitor complexes conducted using selected GyrB/ParE orthologs aided in the identification of important steric, dynamic and compositional differences in the ATP-binding pockets of the targets, enabling the design of highly potent pyrrolopyrimidine inhibitors with broad enzymatic spectrum and dual targeting activity. 相似文献