全文获取类型
收费全文 | 5586篇 |
免费 | 511篇 |
国内免费 | 1篇 |
出版年
2023年 | 28篇 |
2022年 | 75篇 |
2021年 | 135篇 |
2020年 | 83篇 |
2019年 | 114篇 |
2018年 | 119篇 |
2017年 | 104篇 |
2016年 | 172篇 |
2015年 | 317篇 |
2014年 | 329篇 |
2013年 | 406篇 |
2012年 | 497篇 |
2011年 | 479篇 |
2010年 | 281篇 |
2009年 | 250篇 |
2008年 | 353篇 |
2007年 | 325篇 |
2006年 | 298篇 |
2005年 | 330篇 |
2004年 | 301篇 |
2003年 | 255篇 |
2002年 | 217篇 |
2001年 | 46篇 |
2000年 | 34篇 |
1999年 | 44篇 |
1998年 | 49篇 |
1997年 | 29篇 |
1996年 | 32篇 |
1995年 | 21篇 |
1994年 | 37篇 |
1993年 | 22篇 |
1992年 | 27篇 |
1991年 | 25篇 |
1990年 | 14篇 |
1989年 | 14篇 |
1988年 | 11篇 |
1987年 | 15篇 |
1986年 | 21篇 |
1985年 | 10篇 |
1984年 | 22篇 |
1983年 | 9篇 |
1982年 | 10篇 |
1981年 | 7篇 |
1980年 | 11篇 |
1979年 | 12篇 |
1978年 | 9篇 |
1977年 | 26篇 |
1976年 | 12篇 |
1972年 | 9篇 |
1971年 | 11篇 |
排序方式: 共有6098条查询结果,搜索用时 31 毫秒
941.
Background
Halibuts are commercially important flatfish species confined to the North Pacific and North Atlantic Oceans. We have determined the complete mitochondrial genome sequences of four specimens each of Atlantic halibut (Hippoglossus hippoglossus), Pacific halibut (Hippoglossus stenolepis) and Greenland halibut (Reinhardtius hippoglossoides), and assessed the nucleotide variability within and between species.Results
About 100 variable positions were identified within the four specimens in each halibut species, with the control regions as the most variable parts of the genomes (10 times that of the mitochondrial ribosomal DNA). Due to tandem repeat arrays, the control regions have unusually large sizes compared to most vertebrate mtDNAs. The arrays are highly heteroplasmic in size and consist mainly of different variants of a 61-bp motif. Halibut mitochondrial genomes lacking arrays were also detected.Conclusion
The complexity, distribution, and biological role of the heteroplasmic tandem repeat arrays in halibut mitochondrial control regions are discussed. We conclude that the most plausible explanation for array maintenance includes both the slipped-strand mispairing and DNA recombination mechanisms. 相似文献942.
Marine?Goffinet Patrick?Chinestra Isabelle?Lajoie-Mazenc Claire?Medale-Giamarchi Gilles?FavreEmail author Jean-Charles?FayeEmail author 《BMC biotechnology》2008,8(1):34
Background
The Rho GTPases A, B and C proteins, members of the Rho family whose activity is regulated by GDP/GTP cycling, function in many cellular pathways controlling proliferation and have recently been implicated in tumorigenesis. Although overexpression of Rho GTPases has been correlated with tumorigenesis, only their GTP-bound forms are able to activate the signalling pathways implicated in tumorigenesis. Thus, the focus of much recent research has been to identify biological tools capable of quantifying the level of cellular GTP-bound Rho, or determining the subcellular location of activation. However useful, these tools used to study the mechanism of Rho activation still have limitations. The aim of the present work was to employ phage display to identify a conformationally-specific single chain fragment variable (scFv) that recognizes the active, GTP-bound, form of Rho GTPases and is able to discriminate it from the inactive, GDP-bound, Rho in endogenous settings. 相似文献943.
944.
945.
Holmes CP Li X Pan Y Xu C Bhandari A Moody CM Miguel JA Ferla SW De Francisco MN Frederick BT Zhou S Macher N Jang L Irvine JD Grove JR 《Bioorganic & medicinal chemistry letters》2008,18(8):2719-2724
We have synthesized and evaluated a series of triaryl sulfonamide-based PTP1B inhibitors in which a difluoro-methylenephosphonate group of a potent lead has been replaced by potential bioisosteric replacements. Several mono- or di-charged compounds (8a, 8b, and 15a) were shown exhibit inhibitory activity in the low micromolar range, demonstrating the feasibility of using this approach in identifying non-phosphonate pTyr mimetics in a small molecular scaffold. These results also provide a useful indication of the relative effectiveness of these pTyr mimetics. 相似文献
946.
Pagé D Balaux E Boisvert L Liu Z Milburn C Tremblay M Wei Z Woo S Luo X Cheng YX Yang H Srivastava S Zhou F Brown W Tomaszewski M Walpole C Hodzic L St-Onge S Godbout C Salois D Payza K Payza K 《Bioorganic & medicinal chemistry letters》2008,18(13):3695-3700
The preparation and evaluation of a novel class of CB2 agonists based on a benzimidazole moiety are reported. They showed binding affinities up to 1nM towards the CB2 receptor with partial to full agonist potencies. They also demonstrated good to excellent selectivity (>1000-fold) over the CB1 receptor. 相似文献
947.
Structural analysis of oxazolomycin and simpler fragments containing a common 3-hydroxy-2,2-dimethylpropanamide moiety has indicated that a U-shaped conformation is preferred, in some cases stabilised by hydrogen bonding between the N–H and O–H residues, as shown by a combination of molecular modelling, NMR spectroscopic and single crystal X-ray analysis. A direct synthesis of this unit has been established via the opening of β-lactones by a range of amines, and their antibacterial activity been shown to vary with the hydrophobic character of the substituents. 相似文献
948.
Menear KA Adcock C Alonso FC Blackburn K Copsey L Drzewiecki J Fundo A Le Gall A Gomez S Javaid H Lence CF Martin NM Mydlowski C Smith GC 《Bioorganic & medicinal chemistry letters》2008,18(14):3942-3945
We have previously described poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors based on a substituted benzyl-phthalazinone scaffold. As an alternative chemical template, a novel series of alkoxybenzamides were developed with restricted conformation through intramolecular hydrogen bond formation; the compounds exhibit low nM enzyme and cellular activity as PARP-1 inhibitors. 相似文献
949.
Dynamics of a memory trace: effects of sleep on consolidation 总被引:2,自引:0,他引:2
BACKGROUND: There is evidence that sleep is important for memory consolidation, but the underlying neuronal changes are not well understood. We studied the effect of sleep modulation on memory and on neuronal activity in a memory system of the domestic chick brain after the learning process of imprinting. Neurons in this system become, through imprinting, selectively responsive to a training (imprinting) stimulus and so possess the properties of a memory trace. RESULTS: The proportion of neurons responsive to the training stimulus reaches a maximum the day after training. We demonstrate that sleep is necessary for this maximum to be achieved, that sleep stabilizes the initially unstable, selective responses of neurons to the imprinting stimulus, and that for sleep to be effective, it must occur during a particular period of time after training. During this period, there is a time-dependent increase in EEG activity in the 5-6 Hz band, that is, in the lower range of the theta bandwidth. The effects of sleep disturbance on consolidation cannot be attributed to fatigue or to stress. CONCLUSIONS: We establish that long-term trace consolidation requires sleep within a restricted period shortly after learning. Undisturbed sleep is necessary for the stabilization of long-term memory, measured at the behavioral and neuronal levels, and of long-term but not short-term neuronal responsiveness to the training stimulus. 相似文献
950.
Desbois N Gardette M Papon J Labarre P Maisonial A Auzeloux P Lartigue C Bouchon B Debiton E Blache Y Chavignon O Teulade JC Maublant J Madelmont JC Moins N Chezal JM 《Bioorganic & medicinal chemistry》2008,16(16):7671-7690
Various iodo-acridone and acridine carboxamides have been prepared and evaluated as agents for targeted radionuclide and/or chemotherapy for melanoma, due to their structural similarity to benzamides which are known to possess specific affinity for melanin. Three of these carboxamides selected for their in vitro cytotoxic properties were radioiodinated with [(125)I]NaI at high specific activity. Biodistribution studies carried out in B16F0 murine melanoma tumour-bearing mice highlighted that acridone 8f and acridine 9d, presented high, long-lasting tumour concentrations together with an in vivo kinetic profile favourable to application in targeted radionuclide therapy. 相似文献