全文获取类型
收费全文 | 507篇 |
免费 | 130篇 |
出版年
2023年 | 2篇 |
2022年 | 2篇 |
2021年 | 4篇 |
2019年 | 4篇 |
2018年 | 4篇 |
2017年 | 2篇 |
2016年 | 6篇 |
2015年 | 19篇 |
2014年 | 13篇 |
2013年 | 36篇 |
2012年 | 22篇 |
2011年 | 13篇 |
2010年 | 18篇 |
2009年 | 8篇 |
2008年 | 24篇 |
2007年 | 28篇 |
2006年 | 18篇 |
2005年 | 18篇 |
2004年 | 26篇 |
2003年 | 28篇 |
2002年 | 32篇 |
2001年 | 16篇 |
2000年 | 15篇 |
1999年 | 16篇 |
1998年 | 7篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 4篇 |
1994年 | 6篇 |
1993年 | 4篇 |
1992年 | 16篇 |
1991年 | 19篇 |
1990年 | 22篇 |
1989年 | 23篇 |
1988年 | 19篇 |
1987年 | 21篇 |
1986年 | 19篇 |
1985年 | 14篇 |
1984年 | 23篇 |
1983年 | 18篇 |
1982年 | 6篇 |
1981年 | 10篇 |
1980年 | 6篇 |
1979年 | 3篇 |
1978年 | 2篇 |
1977年 | 4篇 |
1976年 | 4篇 |
1972年 | 1篇 |
1967年 | 1篇 |
1963年 | 1篇 |
排序方式: 共有637条查询结果,搜索用时 46 毫秒
1.
P C de Visser N M A J Kriek P A V van Hooft A Van Schepdael D V Filippov G A van der Marel H S Overkleeft J H van Boom D Noort 《The journal of peptide research》2003,61(6):298-306
As part of a program towards the development of novel antibiotics, a convenient method for solid-phase synthesis of the cyclic cationic peptide polymyxin B1 and analogues thereof is described. The methodology, based on cleavage-by-cyclization using Kenner's safety-catch linker, yields crude products with purities ranging from 37-67%. Antibacterial assays revealed that analogues 23-26, in which the (S)-6-methyloctanoic acid moiety is replaced with shorter acyl chains, exhibit distinct antimicrobial activity. The results suggest that the length of the acyl chain is rather critical for antimicrobial activity. On the other hand, substitution of the hydrophobic ring-segment D-Phe-6/Leu-7 in polymyxin B1 with dipeptide mimics (i.e. analogues 27-33) resulted in almost complete loss of antimicrobial activity. 相似文献
2.
M J Blommers H J Slot G A van der Marel J H van Boom C W Hilbers 《Journal of biomolecular structure & dynamics》1990,8(2):233-251
The conformational properties of the cyclic dinucleotide d less than pApA greater than were studied by means of molecular mechanics calculations in which a multiconformation analysis was combined with minimum energy calculations. In this approach models of possible conformers are built by varying the torsion angles of the molecule systematically. These models are then subjected to energy minimization; in the present investigation use was made of the AMBER Force field. It followed that the lowest energy conformer has a pseudo-two-fold axis of symmetry. In this conformer the deoxyribose sugars adopt a N-type conformation. The conformation of the sugar-phosphate backbone is determined by the following torsion angles: alpha +, beta t, gamma +, epsilon t and zeta +. The conformation of this ringsystem corresponds to the structure derived earlier by means of NMR spectroscopy and X-ray diffraction. The observation of a preference for N-type sugar conformations in this molecule can be explained by the steric hindrance induced between opposite H3' atoms when one sugar is switched from N- to S-type puckers. The sugars can in principle switch from N- to S-type conformations, but this requires at least the transition of gamma + to gamma -. In this process the molecule obtains an extended shape in which the bases switch from a pseudo-axial to a pseudo-equatorial position. The calculations demonstrate that, apart from the results obtained for the lowest energy conformation, the 180 degrees change in the propagation direction of the phosphate backbone can be achieved by several different combinations of the backbone torsion angles. It appeared that in the low energy conformers five higher order correlations are found. The combination of torsion angles which are involved in changes in the propagation direction of the sugar-phosphate backbone in DNA-hairpin loops and in tRNA, are found in the dataset obtained for cyclic d less than pApA greater than. It turns out, that in the available examples, 180 degrees changes in the backbone direction are localized between two adjacent nucleotides. 相似文献
3.
Real-time gait assessment utilizing a new way of accelerometry 总被引:1,自引:0,他引:1
Real-time registration of body segment angles is essential in artificial body position control. A new method is presented for the real-time calculation of the lower extremity angles using data obtained from pairs of two one-dimensional accelerometers. It is shown that, assuming rigid-body dynamics and simple hinge joints, relative angles (i.e. angles between segments) can be calculated without integration, thereby solving the problem of integration drift normally associated with accelerometry. During the stance phase of walking, the relative angles can be transformed to absolute angles (i.e. relative to the gravitational field direction) for the different leg segments. The feasibility of relative angle calculation is demonstrated by calculation of the knee angle of a healthy subject. Stability and resolution were demonstrated with measurements during standing. Measurements during standing up, sitting down and walking showed that shock (heel-strike) and skin movements, due to movements of the underlying muscle tissue, are the main error sources. Additional signal processing, e.g. low-pass filtering, can be used to diminish this error. The accuracy of the knee angle found is shown to be high enough to be used in a feedback controller for functional electrostimulation of the lower extremities. 相似文献
4.
5.
L J Rinkel G A van der Marel J H van Boom C Altona 《European journal of biochemistry》1987,163(2):287-296
The solution conformations of the oligonucleotides d(C-C-G-A-A-T-T-C-G-G) and d(C-C-G-A-m6A-T-T-C-G-G) as a function of temperature and sample concentration were investigated by means of 1H-NMR spectroscopy. The NMR spectra revealed that, at certain combinations of temperature and low sample and salt concentration, both compounds exist as a B-DNA-type duplex slowly (on the 1H-NMR time scale) interconverting with a monomeric species. From chemical shift data and imino-proton spectra, it is concluded that the monomeric species consists of a mixture of a hairpin form in rapid equilibrium with the random-coil form. The double-helical stem of the hairpin is formed by the six terminal cytidine and guanine residues, whereas the four core residues, -A-(m6)A-T-T-, partake in the loop. Thermodynamic analysis of the chemical shift of the resonances of the monomeric species vs temperature profiles of the two decamers and mutual comparison of these profiles indicate the following: the influence of N6-methylation of residue A(5) upon the local structure of the hairpin must be small; methylation decreases the stability of the duplex relative to the monomeric species: the temperature at which the fraction duplex equals 0.5 was found to be 312 K for the parent compound and 305 K for the methylated decamer at 2 mM sample concentration; methylation does not significantly alter the stability of the hairpin form relative to the random coil form: the Tm of the hairp----n equilibrium random-coil equilibrium is 308 K for the parent compound and 306 K for the methylated decamer. A higher fraction hairpin-like structure for the N6-methylated compound is observed under identical conditions of temperature and sample concentration: at 300 K, 2 mM sample concentration, the fraction hairpin form is 0.12 for d(C-C-G-A-A-T-T-C-G-G) and 0.20 for d(C-C-G-A-m6A-T-T-C-G-G). This finding appears to be a consequence of the reduced stability of the methylated dimeric species relative to the monomeric species, and to depend upon the sodium-ion concentration: it becomes more pronounced under low-salt conditions. 相似文献
6.
Amplification of chirality based upon the association of nucleic acid strands of opposite handedness
C. A. A. van Boeckel G. M. Visser R. A. Hegstrom J. H. van Boom 《Journal of molecular evolution》1987,25(2):100-105
Summary It is proposed that nucleotide strands of opposite handedness may strongly associate and thereby provide the key step of a mechanism for the amplification of a small enantiomeric excess in an initially near-racemic mixture of poly- or oligonucleotides. This hypothesis, if confirmed by experimentation, may have important implications for the question of the origin of biomolecular chirality. The results of preliminary NMR experiments are given, which do show evidence of a strong association between pentanucleotide RNA strands whose monomers have opposite chirality. Simple kinetic equations are solved to demonstrate the conditions under which such association can produce amplification of chirality. 相似文献
7.
8.
Brian M. Boom 《Brittonia》1989,41(2):129-130
Pagamea aracaënsis Boom, endemic to Serra Aracá, Brazil is described and illustrated, and its relationship toP. anisophylla Standley & Steyerm, is discussed. 相似文献
9.
We have investigated the differences between nuclear genomes of two purportedly congeneric species of sea urchin that differ radically in early development. Heliocidaris tuberculata develops by means of a typical pluteus larva, whereas H. erythrogramma develops directly from an egg that is 100-fold the volume of the H. tuberculata egg. Reassociation kinetic analysis shows that the kinetic components of the genomic DNA from the two species are essentially the same. No single repeat component explains the 30% difference between the H. erythrogramma and H. tuberculata genomes. Reciprocal hybridization of tracer-labeled single-copy DNA fractions between these species indicates that approximately 50% of the single-copy DNA is sufficiently similar to form hybrids at standard hybridization criterion. Thermal denaturation profiles of the hybridized single-copy DNA sequence yields median (T50H) values of 13.8 degrees-16.5 degrees C. This result suggests a divergence time of 10-13 Mya, which is comparable to divergence times between congeneric sea urchin species in other genera that do not differ significantly in development. Radical differences in early developmental processes can evolve rapidly between closely related forms. 相似文献
10.
Solution conformation of an oligonucleotide containing a G.G mismatch determined by nuclear magnetic resonance and molecular mechanics. 总被引:2,自引:1,他引:1 下载免费PDF全文
J A Cognet J Gabarro-Arpa M Le Bret G A van der Marel J H van Boom G V Fazakerley 《Nucleic acids research》1991,19(24):6771-6779
We have determined by two-dimensional nuclear magnetic resonance studies and molecular mechanics calculations the three dimensional solution structure of the non-selfcomplementary oligonucleotide, d(GAGGAGGCACG). d(CGTGCGTCCTC) in which the central base pair is G.G. This is the first structural determination of a G.G mismatch in a oligonucleotide. Two dimensional nuclear magnetic resonance spectra show that the bases of the mismatched pair are stacked into the helix and that the helix adopts a classical B-DNA form. Spectra of the exchangeable protons show that the two guanosines are base paired via their imino protons. For the non-exchangeable protons and for some of the exchangeable protons nuclear Overhauser enhancement build up curves at short mixing times have been measured. These give 84 proton-proton distances which are sensitive to the helix conformation. One of the guanosines adopts a normal anti conformation while the other is syn or close to syn. All non-terminal sugars are C2' endo. These data sets were incorporated into the refinement of the oligonucleotide structure by molecular mechanics calculations. The G.G mismatch shows a symmetrical base pairing structure. Although the mismatch is very bulky many of its features are close to that of normal B-DNA. The mismatch induces a small lateral shift in the helix axis and the sum of the helical twist above and below the mismatch is close to that of B-DNA. 相似文献