全文获取类型
收费全文 | 1219篇 |
免费 | 43篇 |
国内免费 | 1篇 |
专业分类
1263篇 |
出版年
2022年 | 6篇 |
2018年 | 11篇 |
2017年 | 12篇 |
2016年 | 16篇 |
2015年 | 20篇 |
2014年 | 40篇 |
2013年 | 55篇 |
2012年 | 55篇 |
2011年 | 59篇 |
2010年 | 47篇 |
2009年 | 32篇 |
2008年 | 64篇 |
2007年 | 60篇 |
2006年 | 59篇 |
2005年 | 49篇 |
2004年 | 67篇 |
2003年 | 44篇 |
2002年 | 64篇 |
2001年 | 19篇 |
2000年 | 18篇 |
1999年 | 9篇 |
1998年 | 18篇 |
1997年 | 14篇 |
1996年 | 18篇 |
1995年 | 7篇 |
1994年 | 16篇 |
1993年 | 8篇 |
1992年 | 15篇 |
1991年 | 9篇 |
1990年 | 11篇 |
1989年 | 8篇 |
1988年 | 15篇 |
1987年 | 13篇 |
1986年 | 9篇 |
1985年 | 12篇 |
1984年 | 21篇 |
1983年 | 20篇 |
1982年 | 15篇 |
1981年 | 28篇 |
1980年 | 24篇 |
1979年 | 12篇 |
1978年 | 27篇 |
1977年 | 12篇 |
1976年 | 18篇 |
1975年 | 16篇 |
1974年 | 14篇 |
1973年 | 9篇 |
1968年 | 8篇 |
1964年 | 8篇 |
1961年 | 5篇 |
排序方式: 共有1263条查询结果,搜索用时 15 毫秒
41.
42.
Veronika Slancarova Jana Zdanska Bohuslav Janousek Martina Talianova Christian Zschach Jitka Zluvova Jiri Siroky Viera Kovacova Hana Blavet Jiri Danihelka Bengt Oxelman Alex Widmer Boris Vyskot 《Evolution; international journal of organic evolution》2013,67(12):3669-3677
The plant genus Silene has become a model for evolutionary studies of sex chromosomes and sex‐determining mechanisms. A recent study performed in Silene colpophylla showed that dioecy and the sex chromosomes in this species evolved independently from those in Silene latifolia, the most widely studied dioecious Silene species. The results of this study show that the sex‐determining system in Silene otites, a species related to S. colpophylla, is based on female heterogamety, a sex determination system that is unique among the Silene species studied to date. Our phylogenetic data support the placing of S. otites and S. colpophylla in the subsection Otites and the analysis of ancestral states suggests that the most recent common ancestor of S. otites and S. colpophylla was most probably dioecious. These observations imply that a switch from XX/XY sex determination to a ZZ/ZW system (or vice versa) occurred in the subsection Otites. This is the first report of two different types of heterogamety within one plant genus of this mostly nondioecious plant family. 相似文献
43.
Saturation mutagenesis is a powerful tool in protein engineering. Even though QuikChange site-directed mutagenesis method is dominantly used in laboratories, it could not be successfully applied to the generation of a focused mutant library of human glutathione transferase A2-2. In the present study, we further developed an improved versatile dual-tube approach of randomizing difficult-to-amplify targets, exhibiting significant improvement towards equal distribution of nucleotides at randomized sites compared to other published methods. 相似文献
44.
45.
Sjöstrand D Carlsson J Paratcha G Persson B Ibáñez CF 《The Journal of biological chemistry》2007,282(17):12734-12740
Most plasma membrane proteins are capable of sensing multiple cell-cell and cell-ligand interactions, but the extent to which this functional versatility is founded on their modular design is less clear. We have identified the third immunoglobulin domain of the Neural Cell Adhesion Molecule (NCAM) as the necessary and sufficient determinant for its interaction with Glial Cell Line-derived Neurotrophic Factor (GDNF). Four charged contacts were identified by molecular modeling as the main contributors to binding energy. Their mutation abolished GDNF binding to NCAM but left intact the ability of NCAM to mediate cell adhesion, indicating that the two functions are genetically separable. The GDNF-NCAM interface allows complex formation with the GDNF family receptor alpha1, shedding light on the molecular architecture of a multicomponent GDNF receptor. 相似文献
46.
The binding of penetratin, a peptide that has been found useful for cellular delivery of large hydrophilic molecules, to negatively charged vesicles was investigated. The surface charge density of the vesicles was varied by mixing zwitterionic dioleoylphosphatidylcholine (DOPC) and negatively charged dioleoylphosphatidylglycerol (DOPG) at various molar ratios. The extent of membrane association was quantified from tryptophan emission spectra recorded during titration of peptide solution with liposomes. A singular value decomposition of the spectral data demonstrated unambiguously that two species, assigned as peptide free in solution and membrane-bound peptide, respectively, account for the spectral data of the titration series. Binding isotherms were then constructed by least-squares projection of the titration spectra on reference spectra of free and membrane-bound peptide. A model based on the Gouy-Chapman theory in combination with a two-state surface partition equilibrium, separating the electrostatic and the hydrophobic contributions to the binding free energy, was found to be in excellent agreement with the experimental data. Using this model, a surface partition constant of approximately 80 M(-)(1) was obtained for the nonelectrostatic contribution to the binding of penetratin irrespective of the fraction of negatively charged lipids in the membrane, indicating that the hydrophobic interactions are independent of the surface charge density. In accordance with this, circular dichroism measurements showed that the secondary structure of membrane-associated penetratin is independent of the DOPC/DOPG ratio. Experiments using vesicles with entrapped carboxyfluorescein showed that penetratin does not form membrane pores. Studies of the cationic peptide penetratin are complicated by extensive adsorption to surfaces of quartz and plastics. By modification of the quartz cell walls with the cationic polymer poly(ethylenimine), the peptide adsorption was reduced to a tolerable level. The data analysis method used for construction of the binding isotherms eliminated errors emanating from the remaining peptide adsorption, which otherwise would prevent a proper quantification of the binding. 相似文献
47.
Joseph M. Autry John E. Rubin Bengt Svensson Ji Li David D. Thomas 《The Journal of biological chemistry》2012,287(46):39070-39082
We have used fluorescence spectroscopy, molecular modeling, and limited proteolysis to examine structural dynamics of the sarcoplasmic reticulum Ca-ATPase (SERCA). The Ca-ATPase in sarcoplasmic reticulum vesicles from fast twitch muscle (SERCA1a isoform) was selectively labeled with fluorescein isothiocyanate (FITC), a probe that specifically reacts with Lys-515 in the nucleotide-binding site. Conformation-specific proteolysis demonstrated that FITC labeling does not induce closure of the cytoplasmic headpiece, thereby assigning FITC-SERCA as a nucleotide-free enzyme. We used enzyme reverse mode to synthesize FITC monophosphate (FMP) on SERCA, producing a phosphorylated pseudosubstrate tethered to the nucleotide-binding site of a Ca2+-free enzyme (E2 state to prevent FMP hydrolysis). Conformation-specific proteolysis demonstrated that FMP formation induces SERCA headpiece closure similar to ATP binding, presumably due to the high energy phosphoryl group on the fluorescent probe (ATP·E2 analog). Subnanosecond-resolved detection of fluorescence lifetime, anisotropy, and quenching was used to characterize FMP-SERCA (ATP·E2 state) versus FITC-SERCA in Ca2+-free, Ca2+-bound, and actively cycling phosphoenzyme states (E2, E1, and EP). Time-resolved spectroscopy revealed that FMP-SERCA exhibits increased probe dynamics but decreased probe accessibility compared with FITC-SERCA, indicating that ATP exhibits enhanced dynamics within a closed cytoplasmic headpiece. Molecular modeling was used to calculate the solvent-accessible surface area of FITC and FMP bound to SERCA crystal structures, revealing a positive correlation of solvent-accessible surface area with quenching but not anisotropy. Thus, headpiece closure is coupled to substrate binding but not active site dynamics. We propose that dynamics in the nucleotide-binding site of SERCA is important for Ca2+ binding (distal allostery) and phosphoenzyme formation (direct activation). 相似文献
48.
49.
The polysaccharide antigen produced by Eubacterium saburreum, strain L 49, is composed of D-glycero-D-galacto-heptose and a new sugar, tentatively identified as 6-deoxy-D-altro-heptose. It contains chains of alternating (1 leads to 3)- and (1 leads to 6)- linked beta-D-glycero-D-galacto-heptopyranosyl residues, the latter being substituted with 6-deoxy-alpha-heptofuranosyl groups at O-3. The polysaccharide further contains 0-acetyl groups, linked to O-7 of part of the heptosyl residues and to O-2 of part of the 6-deoxyheptosyl groups. 相似文献
50.
Michael K. Bach John R. Brashler Sven Hammarström Bengt Samuelsson 《Biochemical and biophysical research communications》1980,93(4):1121-1126
Slow reacting substance (SRS), produced by rat peritoneal mononuclear cells after stimulation with ionophore A23187, consists of two main components (Bach, M.K. et al. (1979) J. Immunol. 122, 160–165). One of these components was recently identified as leukotriene C-1. The other component has now been identified as leukotriene D. 相似文献