全文获取类型
收费全文 | 1060篇 |
免费 | 103篇 |
专业分类
1163篇 |
出版年
2023年 | 8篇 |
2022年 | 19篇 |
2021年 | 38篇 |
2020年 | 16篇 |
2019年 | 18篇 |
2018年 | 36篇 |
2017年 | 21篇 |
2016年 | 45篇 |
2015年 | 50篇 |
2014年 | 66篇 |
2013年 | 62篇 |
2012年 | 78篇 |
2011年 | 87篇 |
2010年 | 32篇 |
2009年 | 29篇 |
2008年 | 47篇 |
2007年 | 56篇 |
2006年 | 54篇 |
2005年 | 44篇 |
2004年 | 50篇 |
2003年 | 41篇 |
2002年 | 38篇 |
2001年 | 10篇 |
2000年 | 25篇 |
1999年 | 15篇 |
1998年 | 6篇 |
1997年 | 6篇 |
1996年 | 13篇 |
1995年 | 10篇 |
1994年 | 10篇 |
1993年 | 9篇 |
1992年 | 18篇 |
1991年 | 6篇 |
1990年 | 8篇 |
1989年 | 8篇 |
1988年 | 6篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1985年 | 3篇 |
1984年 | 6篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1975年 | 4篇 |
1973年 | 3篇 |
1970年 | 3篇 |
1966年 | 3篇 |
1956年 | 3篇 |
1880年 | 2篇 |
排序方式: 共有1163条查询结果,搜索用时 15 毫秒
991.
Yevdokimov YM Salyanov VI Kondrashina OV Borshevsky VI Semenov SV Gasanov AA Reshetov IV Kuznetsov VD Nikiforov VN Akulinichev SV Mordovskoi MV Potashev SI Skorkin VM 《International journal of biological macromolecules》2005,37(4):165-173
Microscopic size particles of the cholesteric double-stranded DNA (RNA) liquid-crystalline dispersions, containing the ions of the rare earth elements in their content, have been obtained for the first time. The properties of these particles differ from those of classical DNA cholesterics noticeably. The local concentration of the rare earth elements in a particle reaches 200 mg/ml. The particles of the liquid-crystalline dispersion of the (DNA-gadolinium) complex maintain the properties for a long time. The combination of the microscopic size of particles, high concentration of gadolinium in particles and their stability opens a way to practical application of this new biomaterial. 相似文献
992.
Shehadi IA Abyzov A Uzun A Wei Y Murga LF Ilyin V Ondrechen MJ 《Journal of bioinformatics and computational biology》2005,3(1):127-143
THEMATICS (Theoretical Microscopic Titration Curves) is a simple, reliable computational predictor of the active sites of enzymes from structure. Our method, based on well-established Finite Difference Poisson-Boltzmann techniques, identifies the ionisable residues with anomalous predicted titration behavior. A cluster of two or more such perturbed residues is a very reliable predictor of the active site. The protein does not have to bear any resemblance in sequence or structure to any previously characterized protein, but the method does require the three-dimensional structure. We now present evidence that THEMATICS can also locate the active site in structures built by comparative modeling from similar structures. Results are given for a total of 21 sets of proteins, including 21 templates and 83 comparative model structures. Detailed results are presented for three sets of orthologous proteins (Triosephosphate isomerase, 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase, and Aspartate aminotransferase) and for one set of human homologues of Aldose reductase with different functions. THEMATICS correctly locates the active site in the model structures. This suggests that the method can be applicable to a much larger set of proteins for which an experimentally determined structure is unavailable. With a few exceptions, the predicted active sites in the comparative model structures are similar to that of the corresponding template structure. 相似文献
993.
Pisareva E Savov V Kujumdzieva A 《Zeitschrift für Naturforschung. C, Journal of biosciences》2005,60(1-2):116-120
Citrinin is a mycotoxin, which is produced by fungi belonging to the genus Monascus, known in biotechnology as producers of azaphilone pigments. The relation between biosynthesis of these secondary metabolites was investigated in different species of the genus Monascus in batch-culture at the following cultivation conditions: T = 28 degrees C, agitation 220 rpm, and a medium, which induce citrinin production, containing ethanol as a carbon source. The screening was carried out with 16 fungal strains and the biosynthesis of citrinin and pigments was monitored quantitatively at the standard conditions mentioned above. Some kinetic parameters of the process have been determined. The values of the growth yield coefficient Y(X/C) were between 0.32 and 0.57. The amount of the extracellular red and orange pigments at the end of cultivation varied for the different strains between 0.09 and 1.33 OU/ mg dry weight, and 0.15 and 0.96 OU/mg dry weight, respectively. The amount of the total pigments measured was between 0.16 and 3.6 OU/mg dry weight, and between 0.21 and 3.39 OU/mg dry weight. The determined ratio 500 nm/400 nm, characterizing the pigment production, ranged between 0.60 and 1.06. Twelve of the investigated strains produced citrinin and pigments, two of them produced only pigments. Two strains were not able to produce neither pigments nor citrinin. Thus, the biosynthesis of citrinin appeared to be strain-specific and does not correlate with the pigments' biosynthesis by the fungal strains belonging to the genus Monascus. 相似文献
994.
Alpha4beta1-dependent adhesion strengthening under mechanical strain is regulated by paxillin association with the alpha4-cytoplasmic domain
下载免费PDF全文
![点击此处可从《The Journal of cell biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Alon R Feigelson SW Manevich E Rose DM Schmitz J Overby DR Winter E Grabovsky V Shinder V Matthews BD Sokolovsky-Eisenberg M Ingber DE Benoit M Ginsberg MH 《The Journal of cell biology》2005,171(6):1073-1084
The capacity of integrins to mediate adhesiveness is modulated by their cytoplasmic associations. In this study, we describe a novel mechanism by which alpha4-integrin adhesiveness is regulated by the cytoskeletal adaptor paxillin. A mutation of the alpha4 tail that disrupts paxillin binding, alpha4(Y991A), reduced talin association to the alpha4beta1 heterodimer, impaired integrin anchorage to the cytoskeleton, and suppressed alpha4beta1-dependent capture and adhesion strengthening of Jurkat T cells to VCAM-1 under shear stress. The mutant retained intrinsic avidity to soluble or bead-immobilized VCAM-1, supported normal cell spreading at short-lived contacts, had normal alpha4-microvillar distribution, and responded to inside-out signals. This is the first demonstration that cytoskeletal anchorage of an integrin enhances the mechanical stability of its adhesive bonds under strain and, thereby, promotes its ability to mediate leukocyte adhesion under physiological shear stress conditions. 相似文献
995.
996.
Vrudhula VM Dasgupta B Boissard CG Gribkoff VK Santone KS Dalterio RA Lodge NJ Starrett JE 《Bioorganic & medicinal chemistry letters》2005,15(19):4286-4290
Quinolinone 1 is a potent maxi-K potassium channel opener. In an effort to design analogs of 1 with a better inhibitory profile toward the CYP2C9 isozyme, the two acidic sites were chemically modified independently to generate a number of analogs. These analogs were evaluated as maxi-K channel openers in vitro using Xenopus laevis oocytes expressing cloned hSlo maxi-K channels. Compounds 15, 17, and 19 showed potent activity as maxi-K channel openers and were further evaluated for inhibition of the activity of the CYP2C9 isozyme. Compounds 17 and 19 showed diminished inhibitory potency against 2C9 and also against a panel of other more common CYP isozymes. 相似文献
997.
998.
Feigelson SW Grabovsky V Shamri R Levy S Alon R 《The Journal of biological chemistry》2003,278(51):51203-51212
Leukocyte integrins must rapidly strengthen their binding to target endothelial sites to arrest rolling adhesions under physiological shear flow. We demonstrate that the integrin-associated tetraspanin, CD81, regulates VLA-4 and VLA-5 adhesion strengthening in monocytes and primary murine B cells. CD81 strengthens multivalent VLA-4 contacts within subsecond integrin occupancy without altering intrinsic adhesive properties to low density ligand. CD81 facilitates both VLA-4-mediated leukocyte rolling and arrest on VCAM-1 under shear flow as well as VLA-5-dependent adhesion to fibronectin during short stationary contacts. CD81 also augments VLA-4 avidity enhancement induced by either chemokine-stimulated Gi proteins or by protein kinase C activation, although it is not required for Gi protein or protein kinase C signaling activities. In contrast to other proadhesive integrin-associated proteins, CD81-promoted integrin adhesiveness does not require its own ligand occupancy or ligation. These results provide the first demonstration of an integrin-associated transmembranal protein that facilitates instantaneous multivalent integrin occupancy events that promote leukocyte adhesion to an endothelial ligand under shear flow. 相似文献
999.
Bonilla WV Pinschewer DD Klenerman P Rousson V Gaboli M Pandolfi PP Zinkernagel RM Salvato MS Hengartner H 《Journal of virology》2002,76(8):3810-3818
The cellular promyelocytic leukemia protein (PML) associates with the proteins of several viruses and in some cases reduces viral propagation in cell culture. To examine the role of PML in vivo, we compared immune responses and virus loads of PML-deficient and control mice infected with lymphocytic choriomeningitis virus (LCMV) and vesicular stomatitis virus (VSV). PML(-/-) mice exhibited accelerated primary footpad swelling reactions to very-low-dose LCMV, higher swelling peaks upon high-dose inoculation, and higher viral loads in the early phase of systemic LCMV infection. T-cell-mediated hepatitis and consequent mortality upon infection with a hepatotropic LCMV strain required 10- to 100-times-lower inocula despite normal cytotoxic T-lymphocyte reactivity in PML(-/-) mice. Furthermore, PML deficiency rendered mice 10 times more susceptible to lethal immunopathology upon intracerebral LCMV inoculation. Accordingly, 10-times-lower VSV inocula elicited specific neutralizing-antibody responses, a replication-based effect not observed with inactivated virus or after immunization with recombinant VSV glycoprotein. These in vivo observations corroborated our results showing more virus production in PML(-/-) fibroblasts. Thus, PML is a contributor to innate immunity, defining host susceptibility to viral infections and to immunopathology. 相似文献
1000.
Di Valentin M Malorni D Maniero AL Agostini G Giacometti G Vianelli A Vannini C Cattaneo AG Brunel LC Carbonera D 《Photosynthesis research》2002,71(1-2):33-44
Chemical oxidation of the chlorosomes from Chloroflexus aurantiacus and Chlorobium tepidum green bacteria produces bacteriochlorophyll radicals, which are characterized by an anomalously narrow EPR signal compared to in vitro monomeric BChl c
.+ [Van Noort PI, Zhu Y, LoBrutto R and Blankenship RE (1997) Biophys J 72: 316–325]. We have performed oxidant concentration and temperature-dependent X-band EPR measurements in order to elucidate the line narrowing mechanism. The linewidth decreases as the oxidant concentration is increased only for Chloroflexus indicating that for this system Heisenberg spin exchange is at least partially responsible for the EPR spectra narrowing. For both species the linewidth is decreasing on increasing the temperature. This indicates that temperature-activated electron transfer is the main narrowing mechanism for BChl radicals in chlorosomes. The extent of the electron transfer process among different BChl molecules has been evaluated and a comparison between the two species representative of the two green bacteria families has been made. In parallel, high frequency EPR experiments have been performed on the oxidized chlorosomes of Chloroflexus and Chlorobium at 110 and 330 GHz in the full temperature range investigated at X-band. The g-tensor components obtained from the simulation of the 330 GHz EPR spectrum from Chlorobium show the same anisotropy as those of monomeric Chl a
.+ [Bratt PJ, Poluektov OG, Thurnauer MC, Krzystek J, Brunel LC, Schrier J, Hsiao YW, Zerner M and Angerhofer A (2000) J Phys Chem B 104: 6973–6977]. The spectrum of Chloroflexus has a nearly axial g-tensor with reduced anisotropy compared to Chlorobium and monomeric Chl a
in vitro. g-tensor values and temperature dependence of the linewidth have been discussed in terms of the differences in the local structure of the chlorosomes of the two families.This revised version was published online in October 2005 with corrections to the Cover Date. 相似文献