全文获取类型
收费全文 | 817篇 |
免费 | 33篇 |
国内免费 | 17篇 |
出版年
2023年 | 9篇 |
2022年 | 7篇 |
2021年 | 8篇 |
2020年 | 9篇 |
2019年 | 15篇 |
2018年 | 23篇 |
2017年 | 16篇 |
2016年 | 23篇 |
2015年 | 27篇 |
2014年 | 41篇 |
2013年 | 73篇 |
2012年 | 27篇 |
2011年 | 42篇 |
2010年 | 37篇 |
2009年 | 45篇 |
2008年 | 54篇 |
2007年 | 50篇 |
2006年 | 47篇 |
2005年 | 39篇 |
2004年 | 36篇 |
2003年 | 37篇 |
2002年 | 21篇 |
2001年 | 12篇 |
2000年 | 12篇 |
1999年 | 7篇 |
1998年 | 9篇 |
1997年 | 13篇 |
1996年 | 16篇 |
1995年 | 13篇 |
1994年 | 10篇 |
1993年 | 6篇 |
1992年 | 6篇 |
1991年 | 8篇 |
1990年 | 6篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1985年 | 2篇 |
1984年 | 5篇 |
1983年 | 10篇 |
1982年 | 7篇 |
1981年 | 7篇 |
1980年 | 5篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1976年 | 2篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有867条查询结果,搜索用时 15 毫秒
1.
《Journal of molecular biology》2021,433(22):167254
Tau is an intrinsically disordered protein implicated in many neurodegenerative diseases. The repeat domain fragment of tau, tau-K18, is known to undergo a disorder to order transition in the presence of lipid micelles and vesicles, in which helices form in each of the repeat domains. Here, the mechanism of helical structure formation, induced by a phospholipid mimetic, sodium dodecyl sulfate (SDS) at sub-micellar concentrations, has been studied using multiple biophysical probes. A study of the conformational dynamics of the disordered state, using photoinduced electron transfer coupled to fluorescence correlation spectroscopy (PET-FCS) has indicated the presence of an intermediate state, I, in equilibrium with the unfolded state, U. The cooperative binding of the ligand (L), SDS, to I has been shown to induce the formation of a compact, helical intermediate (IL5) within the dead time (∼37 µs) of a continuous flow mixer. Quantitative analysis of the PET-FCS data and the ensemble microsecond kinetic data, suggests that the mechanism of induction of helical structure can be described by a U ↔ I ↔ IL5 ↔ FL5 mechanism, in which the final helical state, FL5, forms from IL5 with a time constant of 50–200 µs. Finally, it has been shown that the helical conformation is an aggregation-competent state that can directly form amyloid fibrils. 相似文献
2.
Nahum J. Duker 《Chemico-biological interactions》1986,60(3):265-273
Hydrolytic damages to DNA can occur at physiological conditions. The possible role of DNA conformation on the distribution of such alterations of pyrimidines was investigated. Model compounds used were the synthetic alternating copolymer poly(dG-dC):poly(dG-dC) and the homopolymer poly(dG):poly(dC). Base damages were assayed by paper chromatography using polymers radioactively labeled in cytosine. Conformational changes were assayed by circular dichroic spectral changes. Incubation and heating of the polymers in 1 mM MnCl2 caused the spectral shift reported for the left-handed Z-DNA conformation in the alternating copolymer and the change reported for the triple helix in the homopolymer. After incubation in 85°C, incidences of base damages were compared between the polymers. The presence of manganese reduced depyrimidination in both polymers. Rates of cytosine deamination to uracil were substantial and did not vary among the various conformational states. 相似文献
3.
Biomass production and plant species diversity in grassland in southern England was monitored before and after a change from conventional to organic farming. Our 18-year study, part of the UK's Environmental Change Network long-term monitoring programme, showed that the cessation of artificial fertiliser use on grassland after conversion to organic farming resulted in a decrease in biomass production and an increase in plant species richness. Grassland productivity decreased immediately after fertiliser application ceased, and after two years the annual total biomass production had fallen by over 50%. In the subsequent decade, total annual grassland productivity did not change significantly, and yields reached 31–66% of the levels recorded pre-management change. Plant species richness that had remained stable during the first 5 years of our study under conventional farming, increased by 300% over the following 13 years under organic farm management. We suggest that the change in productivity is due to the altered composition of species within the plots. In the first few years after the change in farming practice, high yielding, nitrogen-loving plants were outcompeted by lower yielding grasses and forbs, and these species remained in the plots in the following years. This study shows that grassland can be converted from an environment lacking in plant species diversity to a relatively species-rich pasture within 10–15 years, simply by stopping or suspending nitrogen additions. We demonstrate that the trade-off for increasing species richness is a decrease in productivity. Grassland in the UK is often not only managed from a conservation perspective, but to also produce a profitable yield. By considering the species composition and encouraging specific beneficial species such as legumes, it may be possible to improve biomass productivity and reduce the trade-off. 相似文献
4.
《Bioorganic & medicinal chemistry》2016,24(8):1778-1785
As part of a selection strategy for artificial nucleic acids (XNA) (to be considered as potential new information systems in vivo), we have carried out a modelling study on cyclohexanyl nucleic acids (CNA) duplexes and hairpins. CNA may form a duplex as well as hairpin structures, having the carbocyclic nucleosides in the 4C1 conformation (with equatorial basis). The geometry of ds CNA is close to that of a HNA:RNA duplex. We demonstrated that CNA triphosphates function as a substrate for polymerases. Modelling experiments indicate that the monomers are probably presented to the polymerase in the 1C4 conformation. 相似文献
5.
《Bioorganic & medicinal chemistry》2014,22(13):3316-3324
Desymmetrization of the pseudochiral (2r)-configured cyclohexane-1,2,3-triamines 8 with dimethyl oxalate led to racemic aminoquinoxaline-2,3-diones 9. Selective introduction of the κ pharmacophoric structural elements pyrrolidine and 3,4-dichlorophenylacetamide with a two-carbon distance afforded conformationally restricted κ agonists 13–15 based on the quinoxaline ring system. In competitive radioligand receptor binding studies the benzylamine 13b, the secondary amine 14b, and the carbamate 15 displayed high κ receptor affinity. The Ki value of the lead compound derived methoxycarbonyl derivative 15 is 9.7 nM. However, the κ affinity of 15 is exceeded by 13b and 14b with a basic functional group instead of the methoxycarbonyl group in 1-position of the quinoxaline system. The chlorine atoms of the dichlorophenylacetyl residue are essential, since the corresponding phenylacetyl analogs show considerably reduced κ affinity. The potent κ ligands 13b, 14b and 15 are selective over the related μ- and δ-opioid receptors, σ1, σ2 and NMDA receptors. In the [35S]GTPγS-binding assay 13b behaved as partial agonist with lower activity than U-69,593. 相似文献
6.
7.
The temperature dependence of the kinetics of the binding of ATP to myosin subfragment-1 was studied by an ATP chase technique in a rapid-flow-quench apparatus: (formula; see text) A temperature range of 30 degrees C to -15 degrees C was obtained with ethylene glycol as antifreeze. The Arrhenius plot of k2 is discontinuous with a jump at 12 degrees C. Above the jump delta H+ = 9.5 kcal/mol, below delta H+ = 28.5 kcal/mol. Few such Arrhenius plots are recorded in the literature but they are predicted from theory. Thus, we explain our results as a phase change of the subfragment 1-ATP system at 12 degrees C. This is in agreement with certain structural studies. 相似文献
8.
To obtain a satisfactory agreement between computed transition temperatures and those determined experimentally, we introduce explicitly water molecules which hydrate the polar headgroup of dipalmitoylphosphatidylethanolamine molecules. The calculated free energy curves as a function of the intermolecular interchain distance and the degree of hydration of the polar groups permit the determination of the transition of the phospholipid system from the gel to the liquid crystalline phase. The detailed structure of the hydration shell is defined using the supermolecular approach. 相似文献
9.
Toshio Kitamoto 《Population Ecology》1972,14(1):129-136
In a natural population of Solidago altissima L., the changes in the spatial pattern of shoots in the course of growth were studied. The results obtained were summarized as follows:
- The spatial pattern changed from clumped to random distribution as plants grew. The change seemed to be resulted from some density-dependent process acting at a small spatial scale, probably the competition for space.
- Large plants tended to distribute themselves more uniformly over the space than the small ones but at the mature stage of growth such a difference was not obviously recognized. The process of appearance of the small-sized plants during successive periods also seemed to be dependent on local density.
- Large plants at the early stage of growth tended to survive better, and there was a positive correlation between initial size and the size at maturity.
- From these results, it is inferred that the change of spatial pattern from clumped to random distribution is largely due to the elimination of small shoots as the result of competition for space among individual shoots.
10.
An empirical projection method is described to predict the magnitudes and signs of two-bond 13C-13C spin-coupling constants (2JCC) in aldopyranosyl rings. The method has been applied primarily to the interpretation of 2JCCC values, although the behavior of 2JCOC has also been examined in light of the new approach, producing results which may prove useful in the conformational analysis of O-glycosidic linkages in oligosaccharides. High-level ab initio calculations of 2JCC values in model compounds were found to be in agreement with the predictions. 相似文献