全文获取类型
收费全文 | 3250篇 |
免费 | 265篇 |
国内免费 | 2篇 |
专业分类
3517篇 |
出版年
2023年 | 8篇 |
2022年 | 44篇 |
2021年 | 56篇 |
2020年 | 45篇 |
2019年 | 55篇 |
2018年 | 75篇 |
2017年 | 63篇 |
2016年 | 96篇 |
2015年 | 157篇 |
2014年 | 175篇 |
2013年 | 190篇 |
2012年 | 276篇 |
2011年 | 237篇 |
2010年 | 176篇 |
2009年 | 146篇 |
2008年 | 205篇 |
2007年 | 236篇 |
2006年 | 200篇 |
2005年 | 179篇 |
2004年 | 202篇 |
2003年 | 149篇 |
2002年 | 137篇 |
2001年 | 29篇 |
2000年 | 21篇 |
1999年 | 18篇 |
1998年 | 34篇 |
1997年 | 20篇 |
1996年 | 22篇 |
1995年 | 20篇 |
1994年 | 20篇 |
1993年 | 14篇 |
1992年 | 11篇 |
1991年 | 11篇 |
1990年 | 8篇 |
1989年 | 15篇 |
1987年 | 5篇 |
1986年 | 7篇 |
1985年 | 6篇 |
1984年 | 11篇 |
1983年 | 7篇 |
1982年 | 10篇 |
1981年 | 9篇 |
1980年 | 11篇 |
1978年 | 5篇 |
1977年 | 6篇 |
1976年 | 5篇 |
1975年 | 7篇 |
1974年 | 6篇 |
1966年 | 5篇 |
1931年 | 6篇 |
排序方式: 共有3517条查询结果,搜索用时 15 毫秒
61.
62.
Benz(othi)azepine (BTZ) derivatives constitute one of three major classes of L-type Ca(2+) channel ligands. Despite intensive experimental studies, no three-dimensional model of BTZ binding is available. Here we have built KvAP- and KcsA-based models of the Ca(v)1.2 pore domain in the open and closed states and used multiple Monte Carlo minimizations to dock representative ligands. In our open channel model, key functional groups of BTZs interact with BTZ-sensing residues, which were identified in previous mutational experiments. The bulky tricyclic moiety occupies interface between domains III and IV, while the ammonium group protrudes into the inner pore, where it is stabilized by nucleophilic C-ends of the pore helices. In the closed channel model, contacts with several ligand-sensing residues in the inner helices are lost, which weakens ligand-channel interactions. An important feature of the ligand-binding mode in both open and closed channels is an interaction between the BTZ carbonyl group and a Ca(2+) ion chelated by the selectivity filter glutamates in domains III and IV. In the absence of Ca(2+), the tricyclic BTZ moiety remains in the domain interface, while the ammonium group directly interacts with a glutamate residue in the selectivity filter. Our model suggests that the Ca(2+) potentiation involves a direct electrostatic interaction between aCa(2+) ion and the ligand rather than an allosteric mechanism. Energy profiles indicate that BTZs can reach the binding site from the domain interface, whereas access through the open activation gate is unlikely, because reorientation of the bulky molecule in the pore is hindered. 相似文献
63.
Ernestas Gaidamauskas Kanokkarn Saejueng Alvin A. Holder Subalita Bharuah Boris A. Kashemirov Debbie C. Crans Charles E. McKenna 《Journal of biological inorganic chemistry》2008,13(8):1291-1299
Metal complexation reactions can be used effectively as sensors to measure concentrations of phosphate and phosphate analogs.
Recently, a method was described for the detection of phosphate or ATP in aqueous solution based on the displacement by these
ligands of pyrocatechol violet (PV) from a putative 2:1 (Yb3+)2PV complex. We have not been able to reproduce this stoichiometry and report this work in order to correct the coordination
chemistry upon which sensor applications are based. In our work, colorimetric and spectrophotometric detection of phosphate
was confirmed qualitatively (blue PV + Yb3+; yellow + Pi); however, the sequence of visual changes on the titration of PV with 2 equiv. of Yb3+ and back titration with ATP as described previously could not be reproduced. In contrast to the linear response to Pi that was reported previously, the absorbance response at 443 or 623 nm was found to be sigmoidal using the recommended 2:1
Yb3+:PV solution (100 μM:50 μM, pH 7, HEPES). Furthermore, both continuous variation titration and molar ratio analysis (Job plot)
experiments are consistent with 1:1, not 2:1, YbPV complex stoichiometry at pH 7 in HEPES buffer, indicating that the deviation
from linearity is produced by excess Yb3+. Indeed, using a 1:1 Yb3+:PV ratio produces a linear response in ΔAbs at 443 or 623 nm on back titration with analyte (phosphate or ATP). In addition,
speciation analysis of the Yb–ATP system demonstrates that a 1:1 complex containing Yb3+ and ATP predominates in solution at μM metal ion and ATP concentrations. Paramagnetic 1H NMR spectroscopy directly establishes the formation of Yb3+–solute complexes in dilute aqueous solution. The 1:1 YbPV complex can be used for the colorimetric measurement of phosphate
and ATP concentrations from ~2 μM.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
相似文献
Charles E. McKenna (Corresponding author)Email: |
64.
Peter Ditte Boris LakatošL’udovít Varečka Martin Šimkovič 《Biochimica et Biophysica Acta (BBA)/General Subjects》2007
The adaptation to extreme concentrations of Ca2+ and its consequence on the properties of the 45Ca2+ transport were studied in submerged mycelia of Trichoderma viride. The adaptation to low [Ca2+]o did not cause changes in kinetic parameters of the 45Ca2+ influx but the adaptation to high [Ca2+]o increased the KM(Ca2+). The Vmax of the 45Ca2+ influx decreased with the age of (non-adapted) mycelia with concomitant decrease of the KM(Ca2+) these changes were prevented in mycelia adapted to high Ca2+. High [Ca2+]o decreased the stimulation by the uncoupler, 3, 3′, 4′, 5-tetrachloro salicylanilide (TCS) (30 μM), as compared to the control, whereas the Ca2+ chelator, EGTA, stimulated it. In the aged mycelia, the stimulation by TCS of the 45Ca2+ influx faded away, in parallel with the activity of the H+-ATPase. The 45Ca2+ efflux from mycelia was affected by TCS in a similar way as the 45Ca2+ influx. The results demonstrate the adaptive responses of transport processes participating in the mycelial Ca2+ homeostasis and ageing are in agreement with a notion that both Ca2+-influx and-efflux are coupled by the H+-homeostasis at the plasma membrane. 相似文献
65.
Allozyme electrophoresis of four sibling parthenogenetic Caucasian rock lizards Darevskia unisexualis, D.uzzelli, D.sapphirina, and D.bendimahiensis found seven clones and five variable loci. The data supported the hypothesis that D.raddei and D.valentini are the parental species of all four parthenogens. Variation patterns in Darevskia were summarized. Species that originated from a single F1 typically consisted of one widespread clone with a few rare clones. Species with multiple origins displayed variation only
slightly higher than species with a single origin. This is contrary to other genera of parthenogenetic lizards, in which cases
massive clonal variations were observed.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
66.
Chou YH Flitney FW Chang L Mendez M Grin B Goldman RD 《Experimental cell research》2007,313(10):2236-2243
Intermediate filament (IF) proteins exist in multiple structural forms within cells including mature IF, short filaments or 'squiggles', and non-filamentous precursors called particles. These forms are interconvertible and their relative abundance is IF type, cell type- and cell cycle stage-dependent. These structures are often associated with molecular motors, such as kinesin and dynein, and are therefore capable of translocating through the cytoplasm along microtubules. The assembly of mature IF from their precursor particles is also coupled to translation. These dynamic properties of IF provide mechanisms for regulating their reorganization and assembly in response to the functional requirements of cells. The recent findings that IF and their precursors are frequently associated with signaling molecules have revealed new functions for IF beyond their more traditional roles as mechanical integrators of cells and tissues. 相似文献
67.
Methods to account for spatial autocorrelation in the analysis of species distributional data: a review 总被引:19,自引:1,他引:19
Carsten F. Dormann Jana M. McPherson Miguel B. Araújo Roger Bivand Janine Bolliger Gudrun Carl Richard G. Davies Alexandre Hirzel Walter Jetz W. Daniel Kissling Ingolf Kühn Ralf Ohlemüller Pedro R. Peres-Neto Björn Reineking Boris Schröder Frank M. Schurr Robert Wilson 《Ecography》2007,30(5):609-628
Species distributional or trait data based on range map (extent‐of‐occurrence) or atlas survey data often display spatial autocorrelation, i.e. locations close to each other exhibit more similar values than those further apart. If this pattern remains present in the residuals of a statistical model based on such data, one of the key assumptions of standard statistical analyses, that residuals are independent and identically distributed (i.i.d), is violated. The violation of the assumption of i.i.d. residuals may bias parameter estimates and can increase type I error rates (falsely rejecting the null hypothesis of no effect). While this is increasingly recognised by researchers analysing species distribution data, there is, to our knowledge, no comprehensive overview of the many available spatial statistical methods to take spatial autocorrelation into account in tests of statistical significance. Here, we describe six different statistical approaches to infer correlates of species’ distributions, for both presence/absence (binary response) and species abundance data (poisson or normally distributed response), while accounting for spatial autocorrelation in model residuals: autocovariate regression; spatial eigenvector mapping; generalised least squares; (conditional and simultaneous) autoregressive models and generalised estimating equations. A comprehensive comparison of the relative merits of these methods is beyond the scope of this paper. To demonstrate each method's implementation, however, we undertook preliminary tests based on simulated data. These preliminary tests verified that most of the spatial modeling techniques we examined showed good type I error control and precise parameter estimates, at least when confronted with simplistic simulated data containing spatial autocorrelation in the errors. However, we found that for presence/absence data the results and conclusions were very variable between the different methods. This is likely due to the low information content of binary maps. Also, in contrast with previous studies, we found that autocovariate methods consistently underestimated the effects of environmental controls of species distributions. Given their widespread use, in particular for the modelling of species presence/absence data (e.g. climate envelope models), we argue that this warrants further study and caution in their use. To aid other ecologists in making use of the methods described, code to implement them in freely available software is provided in an electronic appendix. 相似文献
68.
Switching of membrane organelles between cytoskeletal transport systems is determined by regulation of the microtubule-based transport 下载免费PDF全文
Intracellular transport of membrane organelles occurs along microtubules (MTs) and actin filaments (AFs). Although transport along each type of the cytoskeletal tracks is well characterized, the switching between the two types of transport is poorly understood because it cannot be observed directly in living cells. To gain insight into the regulation of the switching of membrane organelles between the two major transport systems, we developed a novel approach that combines live cell imaging with computational modeling. Using this approach, we measured the parameters that determine how fast membrane organelles switch back and forth between MTs and AFs (the switching rate constants) and compared these parameters during different signaling states. We show that regulation involves a major change in a single parameter: the transferring rate from AFs onto MTs. This result suggests that MT transport is the defining factor whose regulation determines the choice of the cytoskeletal tracks during the transport of membrane organelles. 相似文献
69.
Carbonic anhydrase (CA) activity of pea thylakoids, thylakoid membranes enriched with photosystem I (PSI-membranes), or photosystem
II (PSII-membranes) as well as both supernatant and pellet after precipitation of thylakoids treated with detergent Triton
X-100 were studied. CA activity of thylakoids in the presence of varying concentrations of Triton X-100 had two maxima, at
Triton/chlorophyll (triton/Chl) ratios of 0.3 and 1.0. CA activities of PSI-membranes and PSII-membranes had only one maximum
each, at Triton/Chl ratio 0.3 or 1.0, respectively. Two CAs with characteristics of the membrane-bound proteins and one CA
with characteristics of the soluble proteins were found in the medium after thylakoids were incubated with Triton. One of
the first two CAs had mobility in PAAG after native electrophoresis the same as that of CA residing in PSI-membranes, and
the other CA had mobility the same as the mobility of CA residing in PSII-membranes, but the latter was different from CA
situated in PSII core-complex (Ignatova et al. 2006 Biochemistry (Moscow) 71:525–532). The properties of the “soluble” CA removed from thylakoids were different from the properties
of the known soluble CAs of plant cell: apparent molecular mass was about 262 kD and it was three orders more sensitive to
the specific CA inhibitor, ethoxyzolamide, than soluble stromal CA. The data are discussed as indicating the presence of,
at least, four CAs in pea thylakoids. 相似文献
70.
The osmotic role of nitrate during aftermath growth of Lolium perenne L. cv. Réveille was investigated. Plants were grown from seed in a controlled environment using a liquid medium with 1.0 m M NH4 NO3 as nitrogen source.
Eight-week-old plants were cut 4.0 cm above the root system and then harvested over a 14-day period of regrowth on the same initial nutrient solution, except that nitrate was15 N labelled. Throughout the experimental period, nitrate storage and reduction in roots were low. In stubble and especially in leaves, nitrate accumulated during the first 6 days of regrowth whereas nitrate reduction mainly occurred after this period. Analyses of carbohydrate, chloride and potassium contents in stubble and leaves showed that the accumulation of nitrate osmotically compensated for the decrease in soluble sugars during the first 6 days of regrowth.
The cumulative osmotic potential of sugars, chloride and nitrate in differently treated plants was studied in stubble and leaves. Compared with uncut plants, the lower carbohydrate concentrations found in cut plants regrowing on 1.0 m M NH4 NO3 were compensated for by an accumulation of nitrate. During aftermath growth on low nitrogen nutrition (0.2 m M NH4 NO3 ), chloride replaced nitrate, supporting the proposed osmotic function of nitrate.
It is concluded that nitrate is involved in the osmotic adjustment of ryegrass during regrowth after cutting. 相似文献
Eight-week-old plants were cut 4.0 cm above the root system and then harvested over a 14-day period of regrowth on the same initial nutrient solution, except that nitrate was
The cumulative osmotic potential of sugars, chloride and nitrate in differently treated plants was studied in stubble and leaves. Compared with uncut plants, the lower carbohydrate concentrations found in cut plants regrowing on 1.0 m M NH
It is concluded that nitrate is involved in the osmotic adjustment of ryegrass during regrowth after cutting. 相似文献