全文获取类型
收费全文 | 3107篇 |
免费 | 300篇 |
出版年
2022年 | 23篇 |
2021年 | 40篇 |
2020年 | 19篇 |
2019年 | 31篇 |
2018年 | 27篇 |
2017年 | 37篇 |
2016年 | 55篇 |
2015年 | 85篇 |
2014年 | 96篇 |
2013年 | 112篇 |
2012年 | 144篇 |
2011年 | 181篇 |
2010年 | 107篇 |
2009年 | 91篇 |
2008年 | 120篇 |
2007年 | 125篇 |
2006年 | 114篇 |
2005年 | 134篇 |
2004年 | 134篇 |
2003年 | 126篇 |
2002年 | 101篇 |
2001年 | 138篇 |
2000年 | 111篇 |
1999年 | 89篇 |
1998年 | 34篇 |
1997年 | 25篇 |
1996年 | 25篇 |
1995年 | 21篇 |
1994年 | 26篇 |
1993年 | 30篇 |
1992年 | 75篇 |
1991年 | 66篇 |
1990年 | 72篇 |
1989年 | 83篇 |
1988年 | 60篇 |
1987年 | 64篇 |
1986年 | 60篇 |
1985年 | 45篇 |
1984年 | 49篇 |
1983年 | 36篇 |
1982年 | 23篇 |
1981年 | 28篇 |
1980年 | 33篇 |
1979年 | 43篇 |
1978年 | 21篇 |
1977年 | 25篇 |
1976年 | 30篇 |
1974年 | 26篇 |
1973年 | 17篇 |
1971年 | 23篇 |
排序方式: 共有3407条查询结果,搜索用时 15 毫秒
981.
Synthesis and inhibitory activity of benzoic acid and pyridine derivatives on influenza neuraminidase 总被引:1,自引:0,他引:1
Chand P Kotian PL Morris PE Bantia S Walsh DA Babu YS 《Bioorganic & medicinal chemistry》2005,13(7):2665-2678
Based upon the activity and X-ray crystallographic studies of tri-substituted benzene derivatives containing carboxylic acid, acetamido and guanidine groups, we investigated the effect of the fourth substituent to fulfill the fourth pocket of neuraminidase enzyme. The groups selected as fourth substituents were hydroxymethyl, hydroxyethyl, oxime and amino. These tetra-substituted benzene derivatives were synthesized and evaluated for neuraminidase inhibitory activity. All these compounds were found to have poorer IC(50) values than the tri-substituted compounds. Further, benzene ring was replaced by pyridine ring and di, tri and tetra-substituted pyridine derivatives were synthesized. The activity of the pyridine derivatives was comparable to benzene derivatives. The fourth substituent seems to disturb the binding of the other three substituents, so the activity is reduced as compared to tri-substituted benzene and pyridine derivatives. 相似文献
982.
The modern generation of transthoracic defibrillators now employ impedance compensated biphasic waveforms. These new devices are superior to those with monophasic waveforms and practice is currently switching to biphasic defibrillators for the treatment of both ventricular and atrial fibrillation. However, there is no universal guideline for the use of biphasic defibrillators in direct current cardioversion of atrial fibrillation. This article reviews the use of biphasic defibrillation waveforms for transthoracic cardioversion of atrial fibrillation. 相似文献
983.
Curran DR Morgan RK Kingham PJ Durcan N McLean WG Walsh MT Costello RW 《American journal of physiology. Lung cellular and molecular physiology》2005,288(2):L326-L332
Eosinophils interact with nerve cells, leading to changes in neurotransmitter release, altered nerve growth, and protection from cytokine-induced apoptosis. In part, these interactions occur as a result of activation of neural nuclear factor (NF)-kappaB, which is activated by adhesion of eosinophils to neural intercellular adhesion molecule-1 (ICAM-1). The mechanism and consequence of signaling after eosinophil adhesion to nerve cells were investigated. Eosinophil membranes, which contain eosinophil adhesion molecules but not other eosinophil products, were coincubated with IMR-32 cholinergic nerve cells. The studies showed that there were two mechanisms of activation of NF-kappaB, one of which was dependent on reactive oxygen species, since it was inhibited with diphenyleneiodonium. This occurred at least 30 min after coculture of eosinophils and nerves. An earlier phase of NF-kappaB activation occurred within 2 min of eosinophil adhesion and was mediated by tyrosine kinase-dependent phosphorylation of interleukin-1 receptor-associated kinase-1 (IRAK-1). Coimmunoprecipitation experiments showed that both extracellular signal-regulated kinase 1/2 and IRAK-1 were recruited to ICAM-1 rapidly after coculture with eosinophil membranes. This was accompanied by an induction of ICAM-1, which was mediated by an IRAK-1-dependent pathway. These data indicate that adhesion of eosinophils to IMR-32 nerves via ICAM-1 leads to important signaling events, mediated via IRAK-1, and these in turn lead to expression of adhesion molecules. 相似文献
984.
When it comes to listening to music, infants literally have a more open mind than their parents. Studies which investigate listening behaviour of babies and adults have shown that, as we learn to discriminate the musical sounds in our own environment, we become less sensitive to those of other cultures. 相似文献
985.
Kevin A. Hughes Shaun Walsh Peter Convey Sarah Richards Dana M. Bergstrom 《Polar Biology》2005,28(7):568-570
The populations of two non-native Dipterans have been established at two Antarctic research stations since at least 1998. Both belong to Sciaridae (black fungus midge), and have been determined to the genus Lycoriella. At Rothera Research Station, Antarctic Peninsula, flies are present in the station alcohol bond store, while at Casey Station, on the coast of continental Antarctica, a second Lycoriella sp. is found breeding in the station sewage facilities. Neither species is thought capable of surviving outside the protected environment of the research station buildings, but their establishment highlights the need for strict quarantine controls in order for National Operators in the Antarctic to conform to the Environmental Protocol of the Antarctic Treaty and prevent the introduction of alien species into Antarctica. Protocols for fly eradication are currently being implemented. 相似文献
986.
Importance of arginine 20 of the swine vesicular disease virus 2A protease for activity and virulence 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Inoue T Alexandersen S Clark AT Murphy C Quan M Reid SM Sakoda Y Johns HL Belsham GJ 《Journal of virology》2005,79(1):428-440
A major virulence determinant of swine vesicular disease virus (SVDV), an Enterovirus that causes an acute vesicular disease, has been mapped to residue 20 of the 2A protease. The SVDV 2A protease cleaves the 1D-2A junction in the viral polyprotein, induces cleavage of translation initiation factor eIF4GI, and stimulates the activity of enterovirus internal ribosome entry sites (IRESs). The 2A protease from an attenuated strain of SVDV (Ile at residue 20) is significantly defective at inducing cleavage of eIF4GI and the activation of IRES-dependent translation compared to the 2A protease from a pathogenic strain (J1/73, Arg at residue 20), but the two proteases have similar 1D-2A cleavage activities (Y. Sakoda, N. Ross-Smith, T. Inoue, and G. J. Belsham, J. Virol. 75:10643-10650, 2001). Residue 20 has now been modified to every possible amino acid, and the activities of each mutant 2A protease has been analyzed. Selected mutants were reconstructed into full-length SVDV cDNA, and viruses were rescued. The rate of virus growth in cultured swine kidney cells reflected the efficiency of 2A protease activity. In experimentally infected pigs, all four of the mutant viruses tested displayed much-reduced virulence compared to the J1/73 virus but a significant, albeit reduced, level of viral replication and excretion was detected. Direct sequencing of cDNA derived from samples taken early and late in infection indicated that a gradual selection-reversion to a more efficient protease occurred. The data indicated that extensive sequence change and selection may introduce a severe bottleneck in virus replication, leading to a decreased viral load and reduced or no clinical disease. 相似文献
987.
Carbamazepine is an inhibitor of histone deacetylases 总被引:5,自引:0,他引:5
988.
989.
Williams G Williams EJ Maison P Pangalos MN Walsh FS Doherty P 《The Journal of biological chemistry》2005,280(7):5862-5869
Myelin inhibitors activate a p75(NTR)-dependent signaling cascade in neurons that not only inhibits axonal growth but also prevents neurotrophins (NT) from stimulating growth. Most intriguingly, in addition to Trk receptors, neurotrophins also bind to p75(NTR). We have designed a "mini-neurotrophin" called B(AG) to activate TrkB in the absence of p75(NTR) binding. We find that B(AG) is as effective as the natural TrkB ligands (brain-derived neurotrophic factor (BDNF) and NT-4) at promoting neurite outgrowth from cerebellar neurons. Furthermore, the neurite outgrowth responses stimulated by BDNF and B(AG) are inhibited by a common set of reagents, including the Trk receptor inhibitor K252a, as well as protein kinase A and phosphoinositide 3-kinase inhibitors. However, in contrast to BDNF, B(AG) promotes growth in the presence of a myelin inhibitor or when antibodies directly activate the p75(NTR) inhibitory pathway. On the basis of this observation, we postulated that the binding of BDNF to the p75(NTR) might compromise the ability of BDNF to stimulate neurite outgrowth in an inhibitory environment. To test this, we used NGF, and an NGF-derived peptide, to compete for the BDNF/p75(NTR) interaction; remarkably, in the presence of either agent, BDNF acquired the ability to promote neurite outgrowth in the presence of a myelin inhibitor. The data suggest that in an inhibitory environment, the BDNF/p75(NTR) interaction compromises regeneration. Agents that activate Trk receptors in the absence of p75(NTR) binding, or agents that inhibit neurotrophin/p75(NTR) binding, might therefore be better therapeutic candidates than neurotrophins. 相似文献
990.