全文获取类型
收费全文 | 3190篇 |
免费 | 308篇 |
国内免费 | 6篇 |
出版年
2023年 | 22篇 |
2022年 | 22篇 |
2021年 | 92篇 |
2020年 | 37篇 |
2019年 | 50篇 |
2018年 | 75篇 |
2017年 | 47篇 |
2016年 | 80篇 |
2015年 | 160篇 |
2014年 | 167篇 |
2013年 | 211篇 |
2012年 | 285篇 |
2011年 | 261篇 |
2010年 | 144篇 |
2009年 | 127篇 |
2008年 | 181篇 |
2007年 | 166篇 |
2006年 | 173篇 |
2005年 | 117篇 |
2004年 | 112篇 |
2003年 | 95篇 |
2002年 | 96篇 |
2001年 | 88篇 |
2000年 | 77篇 |
1999年 | 58篇 |
1998年 | 20篇 |
1997年 | 24篇 |
1996年 | 28篇 |
1995年 | 29篇 |
1994年 | 23篇 |
1993年 | 11篇 |
1992年 | 36篇 |
1991年 | 18篇 |
1990年 | 33篇 |
1989年 | 36篇 |
1988年 | 28篇 |
1987年 | 19篇 |
1986年 | 22篇 |
1985年 | 30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 | 13篇 |
排序方式: 共有3504条查询结果,搜索用时 328 毫秒
131.
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
132.
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
133.
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
134.
135.
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
136.
Jasmine Capdor Meika Foster Peter Petocz Samir Samman 《Journal of trace elements in medicine and biology》2013,27(2):137-142
BackgroundImpaired zinc metabolism is prominent in chronic disorders including cardiovascular disease and diabetes. Zinc has the potential to affect glucose homeostasis in animals and humans and hence impact the risk of type 2 diabetes mellitus.MethodsA systematic review and meta-analysis of randomised placebo controlled trials was conducted to determine the effect of zinc supplementation on fasting blood glucose, HbA1c, serum insulin and serum zinc concentrations. Relevant studies for inclusion were identified from a literature search of electronic databases up to July 2011.ResultsFourteen reports (n = 3978 subjects) were included in the meta-analysis. In the overall analysis, a small but statistically significant reduction in fasting glucose concentrations was observed (?0.19 ± 0.08 mmol/L, P = 0.013) after zinc supplementation. HbA1c tended to decrease in zinc-supplemented individuals (?0.64 ± 0.36%, P = 0.072). No significant effect was observed for serum insulin concentrations. Plasma zinc concentrations increased significantly following supplementation (+4.03 ± 0.81 μmol/L, P = 0.001). In secondary analyses of participants with chronic metabolic disease (types 1 and 2 diabetes mellitus, metabolic syndrome and obesity), zinc supplementation produced a greater reduction in glucose concentrations (?0.49 ± 0.11 mmol/L, P = 0.001) compared to the effect that was observed in healthy participants.ConclusionThe significant albeit modest reduction in glucose concentrations and tendency for a decrease in HbA1c following zinc supplementation suggest that zinc may contribute to the management of hyperglycemia in individuals with chronic metabolic disease. 相似文献
137.
138.
V KW Wong T Li B YK Law E DL Ma N C Yip F Michelangeli C KM Law M M Zhang K YC Lam P L Chan L Liu 《Cell death & disease》2013,4(7):e720
Autophagy is an important cellular process that controls cells in a normal homeostatic state by recycling nutrients to maintain cellular energy levels for cell survival via the turnover of proteins and damaged organelles. However, persistent activation of autophagy can lead to excessive depletion of cellular organelles and essential proteins, leading to caspase-independent autophagic cell death. As such, inducing cell death through this autophagic mechanism could be an alternative approach to the treatment of cancers. Recently, we have identified a novel autophagic inducer, saikosaponin-d (Ssd), from a medicinal plant that induces autophagy in various types of cancer cells through the formation of autophagosomes as measured by GFP-LC3 puncta formation. By computational virtual docking analysis, biochemical assays and advanced live-cell imaging techniques, Ssd was shown to increase cytosolic calcium level via direct inhibition of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump, leading to autophagy induction through the activation of the Ca2+/calmodulin-dependent kinase kinase–AMP-activated protein kinase–mammalian target of rapamycin pathway. In addition, Ssd treatment causes the disruption of calcium homeostasis, which induces endoplasmic reticulum stress as well as the unfolded protein responses pathway. Ssd also proved to be a potent cytotoxic agent in apoptosis-defective or apoptosis-resistant mouse embryonic fibroblast cells, which either lack caspases 3, 7 or 8 or had the Bax-Bak double knockout. These results provide a detailed understanding of the mechanism of action of Ssd, as a novel autophagic inducer, which has the potential of being developed into an anti-cancer agent for targeting apoptosis-resistant cancer cells. 相似文献
139.
Lee A. Rollins Angela T. Moles Serena Lam Robert Buitenwerf Joanna M. Buswell Claire R. Brandenburger Habacuc Flores‐Moreno Knud B. Nielsen Ellen Couchman Gordon S. Brown Fiona J. Thomson Frank Hemmings Richard Frankham William B. Sherwin 《Ecology and evolution》2013,3(13):4501-4517
Some introduced populations thrive and evolve despite the presumed loss of diversity at introduction. We aimed to quantify the amount of genetic diversity retained at introduction in species that have shown evidence of adaptation to their introduced environments. Samples were taken from native and introduced ranges of Arctotheca populifolia and Petrorhagia nanteuilii. Using microsatellite data, we identified the source for each introduction, estimated genetic diversity in native and introduced populations, and calculated the amount of diversity retained in introduced populations. These values were compared to those from a literature review of diversity in native, confamilial populations and to estimates of genetic diversity retained at introduction. Gene diversity in the native range of both species was significantly lower than for confamilials. We found that, on average, introduced populations showing evidence of adaptation to their new environments retained 81% of the genetic diversity from the native range. Introduced populations of P. nanteuilii had higher genetic diversity than found in the native source populations, whereas introduced populations of A. populifolia retained only 14% of its native diversity in one introduction and 1% in another. Our literature review has shown that most introductions demonstrating adaptive ability have lost diversity upon introduction. The two species studied here had exceptionally low native range genetic diversity. Further, the two introductions of A. populifolia represent the largest percentage loss of genetic diversity in a species showing evidence of substantial morphological change in the introduced range. While high genetic diversity may increase the likelihood of invasion success, the species examined here adapted to their new environments with very little neutral genetic diversity. This finding suggests that even introductions founded by small numbers of individuals have the potential to become invasive. 相似文献
140.
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