全文获取类型
收费全文 | 414篇 |
免费 | 34篇 |
出版年
2021年 | 6篇 |
2019年 | 4篇 |
2018年 | 7篇 |
2017年 | 4篇 |
2016年 | 8篇 |
2015年 | 21篇 |
2014年 | 14篇 |
2013年 | 20篇 |
2012年 | 21篇 |
2011年 | 22篇 |
2010年 | 17篇 |
2009年 | 18篇 |
2008年 | 27篇 |
2007年 | 16篇 |
2006年 | 19篇 |
2005年 | 12篇 |
2004年 | 19篇 |
2003年 | 12篇 |
2002年 | 14篇 |
2001年 | 15篇 |
2000年 | 16篇 |
1999年 | 16篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 9篇 |
1995年 | 6篇 |
1994年 | 7篇 |
1993年 | 5篇 |
1992年 | 6篇 |
1991年 | 9篇 |
1990年 | 11篇 |
1989年 | 7篇 |
1988年 | 6篇 |
1987年 | 5篇 |
1986年 | 3篇 |
1985年 | 8篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1977年 | 6篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1929年 | 1篇 |
排序方式: 共有448条查询结果,搜索用时 250 毫秒
141.
142.
Toh KC van Stokkum IH Hendriks J Alexandre MT Arents JC Perez MA van Grondelle R Hellingwerf KJ Kennis JT 《Biophysical journal》2008,95(1):312-321
The flavoprotein AppA from Rhodobacter sphaeroides contains an N-terminal, FAD-binding BLUF photoreceptor domain. Upon illumination, the AppA BLUF domain forms a signaling state that is characterized by red-shifted absorbance by 10 nm, a state known as AppARED. We have applied ultrafast spectroscopy on the photoaccumulated AppARED state to investigate the photoreversible properties of the AppA BLUF domain. On light absorption by AppARED, the FAD singlet excited state decays monoexponentially in 7 ps to form the neutral semiquinone radical FADH•, which subsequently decays to the original AppARED molecular ground state in 60 ps. Thus, is deactivated rapidly via electron and proton transfer, probably from the conserved tyrosine Tyr-21 to FAD, followed by radical-pair recombination. We conclude that, in contrast to many other photoreceptors, the AppA BLUF domain is not photoreversible and does not enter alternative reaction pathways upon absorption of a second photon. To explain these properties, we propose that a molecular configuration is formed upon excitation of AppARED that corresponds to a forward reaction intermediate previously identified for the dark-state BLUF photoreaction. Upon excitation of AppARED, the BLUF domain therefore enters its forward reaction coordinate, readily re-forming the AppARED ground state and suppressing reverse or side reactions. The monoexponential decay of FAD* indicates that the FAD-binding pocket in AppARED is significantly more rigid than in dark-state AppA. Steady-state fluorescence experiments on wild-type, W104F, and W64F mutant BLUF domains show tryptophan fluorescence maxima that correspond with a buried conformation of Trp-104 in dark and light states. We conclude that Trp-104 does not become exposed to solvent during the BLUF photocycle. 相似文献
143.
144.
145.
146.
PTPN3 and PTPN4 are two closely-related non-receptor protein tyrosine phosphatases (PTP) that, in addition to a PTP domain, contain FERM (Band 4.1, Ezrin, Radixin, and Moesin) and PDZ (PSD-95, Dlg, ZO-1) domains. Both PTP have been implicated as negative-regulators of early signal transduction through the T cell antigen receptor (TCR), acting to dephosphorylate the TCRζ chain, a component of the TCR complex. Previously, we reported upon the production and characterization of PTPN3-deficient mice which show normal TCR signal transduction and T cell function. To address if the lack of a T cell phenotype in PTPN3-deficient mice can be explained by functional redundancy of PTPN3 with PTPN4, we generated PTPN4-deficient and PTPN4/PTPN3 double-deficient mice. As in PTPN3 mutants, T cell development and homeostasis and TCR-induced cytokine synthesis and proliferation were found to be normal in PTPN4-deficient and PTPN4/PTPN3 double-deficient mice. PTPN13 is another FERM and PDZ domain-containing non-receptor PTP that is distantly-related to PTPN3 and PTPN4 and which has been shown to function as a negative-regulator of T helper-1 (Th1) and Th2 differentiation. Therefore, to determine if PTPN13 might compensate for the loss of PTPN3 and PTPN4 in T cells, we generated mice that lack functional forms of all three PTP. T cells from triple-mutant mice developed normally and showed normal cytokine secretion and proliferative responses to TCR stimulation. Furthermore, T cell differentiation along the Th1, Th2 and Th17 lineages was largely unaffected in triple-mutants. We conclude that PTPN3 and PTPN4 are dispensable for TCR signal transduction. 相似文献
147.
Dario Di Carlo Rasi Koen H. Hendriks Martijn M. Wienk René A. J. Janssen 《Liver Transplantation》2017,7(22)
Triple‐junction device architectures represent a promising strategy to highly efficient organic solar cells. Accurate characterization of such devices is challenging, especially with respect to determining the external quantum efficiency (EQE) of the individual subcells. The specific light bias conditions that are commonly used to determine the EQE of a subcell of interest cause an excess of charge generation in the two other subcells. This results in the build‐up of an electric field over the subcell of interest, which enhances current generation and leads to an overestimation of the EQE. A new protocol, involving optical modeling, is developed to correctly measure the EQE of triple‐junction organic solar cells. Apart from correcting for the build‐up electric field, the effect of light intensity is considered with the help of representative single‐junction cells. The short‐circuit current density (JSC) determined from integration of the EQE with the AM1.5G solar spectrum differs by up to 10% between corrected and uncorrected protocols. The results are validated by comparing the EQE experimentally measured to the EQE calculated via optical‐electronic modeling, obtaining an excellent agreement. 相似文献
148.
Daan M F van Aalten Andrea Haker Johnny Hendriks Klaas J Hellingwerf Leemor Joshua-Tor Wim Crielaard 《The Journal of biological chemistry》2002,277(8):6463-6468
Crystallographic and spectroscopic analyses of three hinge-bending mutants of the photoactive yellow protein are described. Previous studies have identified Gly(47) and Gly(51) as possible hinge points in the structure of the protein, allowing backbone segments around the chromophore to undergo large concerted motions. We have designed, crystallized, and solved the structures of three mutants: G47S, G51S, and G47S/G51S. The protein dynamics of these mutants are significantly affected. Transitions in the photocycle, measured with laser induced transient absorption spectroscopy, show rates up to 6-fold different from the wild type protein and show an additive effect in the double mutant. Compared with the native structure, no significant conformational differences were observed in the structures of the mutant proteins. We conclude that the structural and dynamic integrity of the region around these mutations is of crucial importance to the photocycle and suggest that the hinge-bending properties of Gly(51) may also play a role in PAS domain proteins where it is one of the few conserved residues. 相似文献
149.
We have studied the kinetics of the blue light-induced branching reaction in the photocycle of photoactive yellow protein (PYP) from Ectothiorhodospira halophila, by nanosecond time-resolved UV/Vis spectroscopy. As compared to the parallel dark recovery reaction of the presumed blue-shifted signaling state pB, the light-induced branching reaction showed a 1000-fold higher rate. In addition, a new intermediate was detected in this branching pathway, which, compared to pB, showed a larger extinction coefficient and a blue-shifted absorption maximum. This substantiates the conclusion that isomerization of the chromophore is the rate-controlling step in the thermal photocycle reactions of PYP and implies that absorption of a blue photon leads to cis-->trans isomerization of the 4-hydroxy-cinnamyl chromophore of PYP in its pB state. 相似文献
150.
M. Van Puymbroeck M. E. M. Kuilman R. F. M. Maas R. F. Witkamp L. Leyssens A. S. J. P. A. M. Van Miert L. Hendriks D. Vanderzande P. Adriaensens M. -P. Jacobs J. Raus 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1999,728(2):1289
The metabolism of the illegal growth promoter ethylestrenol (EES) was evaluated in bovine liver cells and subcellular fractions of bovine liver preparations. Incubations with bovine microsomal preparations revealed that EES is extensively biotransformed into norethandrolone (NE), another illegal growth promoter. Furthermore, incubations of monolayer cultures of hepatocytes with NE indicated that NE itself is rapidly reduced to 17α-ethyl-5β-estrane-3α,17β-diol (EED). In vivo tests confirmed that, after administration of either EES or NE, EED is excreted as a major metabolite. Therefore, it was concluded that, both in urine and faeces samples, EED can be used as a biological marker for the illegal use of EES and/or NE. Moreover, by monitoring EED in urine or faeces samples, the detection period after NE administration is significantly prolonged. These findings were further confirmed by three cases of norethandrolone abuse in a routine screening program for forbidden growth promoters. 相似文献