全文获取类型
收费全文 | 4665篇 |
免费 | 469篇 |
出版年
2022年 | 34篇 |
2021年 | 56篇 |
2020年 | 44篇 |
2019年 | 55篇 |
2018年 | 56篇 |
2017年 | 79篇 |
2016年 | 88篇 |
2015年 | 146篇 |
2014年 | 190篇 |
2013年 | 202篇 |
2012年 | 277篇 |
2011年 | 257篇 |
2010年 | 184篇 |
2009年 | 167篇 |
2008年 | 229篇 |
2007年 | 207篇 |
2006年 | 190篇 |
2005年 | 205篇 |
2004年 | 211篇 |
2003年 | 204篇 |
2002年 | 166篇 |
2001年 | 181篇 |
2000年 | 149篇 |
1999年 | 146篇 |
1998年 | 79篇 |
1997年 | 81篇 |
1996年 | 61篇 |
1995年 | 45篇 |
1994年 | 64篇 |
1993年 | 45篇 |
1992年 | 86篇 |
1991年 | 73篇 |
1990年 | 72篇 |
1989年 | 71篇 |
1988年 | 57篇 |
1987年 | 41篇 |
1986年 | 40篇 |
1985年 | 67篇 |
1984年 | 43篇 |
1983年 | 35篇 |
1982年 | 39篇 |
1981年 | 26篇 |
1980年 | 25篇 |
1979年 | 42篇 |
1978年 | 23篇 |
1977年 | 23篇 |
1976年 | 24篇 |
1974年 | 29篇 |
1973年 | 23篇 |
1972年 | 23篇 |
排序方式: 共有5134条查询结果,搜索用时 78 毫秒
221.
222.
223.
Jef Faridi Katrine E. Nielsen Paul C. Stein Jens Peter Jacobsen 《Journal of biomolecular structure & dynamics》2013,31(2):321-332
Abstract We have used one and two dimensional exchange 1H NMR spectroscopy to characterize the dynamics of the binding of a homodimeric thiazole orange dye, 1,1′-(4,4,8,8-tetramethyl-4,8-diaza-undecamethylene)-bis-4-(3-methyl-2,3-dihydro-(benzo-1,3-thiazole)-2-methylidene)-quinolinium tetraiodide (TOTO), to double stranded DNA (dsDNA). The double stranded oligonucleotides used were d-(CGCTAGCG)2 ( 1 ) and d(CGCTAGCTAGCG)2 ( 2 ). TOTO binds preferentially to the (5′-CTAG-3′)2 sites and forms mixtures of 1:1 and 1:2 dsDNA-TOTO complexes with 2 in ratios dependent on the relative amount of TOTO and the oligonucleotide in the sample. The dynamic exchange between preferential binding sites in the case of a 2:1 1 -TOTO mixture is an intermolecular exchange process between two binding sites on different oligonucleotides. In the case of the 1:1 2 -TOTO complex an intramolecular exchange process occur between two different binding sites on the same strand. Both processes were studied. The results demonstrate the ability of TOTO to migrate along a dsDNA strand in an intramolecular exchange process. The migration process (“creeping”) along the DNA strand is 6 times faster than the rate of intermolecular exchange between sites in two different oligonucleotides. 相似文献
224.
Christina B. Nielsen Sanjay K. Singh Jesper Wengel Jens Peter Jacobsen 《Journal of biomolecular structure & dynamics》2013,31(2):175-191
Abstract LNA (Locked Nucleic Acids) is a novel oligonucleotide analogue containing a conformationally restricted nucleotide with a 2′-0, 4′-C-methylene bridge that induces unprecedented thermal affinities when mixed with complementary single stranded DNA and RNA. We have used two-dimensional'H NMR spectroscopy obtained at 750 and 500 MHz to determine a high resolution solution structure of an LNA oligonucleotide hybridized to the complementary DNA strand. The determination of the structure was based on a complete relaxation matrix analysis of the NOESY cross peaks followed by restrained molecular dynamics calculations. Forty final structures were generated for the duplex from A-type and B-type dsDNA starting structures. The root-mean-square deviation (RMSD) of the coordinates for the forty structures of the complex was 0.32Å. The structures were analysed by use of calculated helix parameters. This showed that the values for rise and buckle in the LNA duplex is markedly different from canonical B-DNA at the modification site. A value of twist similar to A-DNA is also observed at the modification site. The overall length of the helix which is 27.3Å. The average twist over the sequence are 35.9° ± 0.3°. Consequently, the modification does not cause the helix to unwind. The bis-intercalation of the thiazole orange dye TOTO to the LNA duplex was also investigated by 1H NMR spectroscopy to sense the structural change from the unmodified oligonucleotide. We observed that the bis-intercalation of TOTO is much less favourable in the 5′-CTLAG-3′ site than in the unmodified 5′-CTLAG-3′ site. This was related to the change in the base stacking of the LNA duplex compared to the unmodified duplex. 相似文献
225.
Sven N. Nielsen 《Pal?ontologische Zeitschrift》2013,87(1):33-66
A new Pliocene (3.4 Ma) mollusk fauna from Mejillones Peninsula, northern Chile is described and compared with the Pliocene La Cueva fauna of little constrained age from central Chile and some species from the Huenteguapi Sandstone overlying the Ranquil Formation on Arauco Peninsula, south central Chile. Preliminary correlation is based on faunal similarities. A total of 45 taxa were identified, of which Cyclocardia kieli sp. nov. is new to science. New combinations are Macron escalonia (Vermeij and DeVries, 1997), Austrofusus steinmanni (Möricke, 1896) and Leukoma antiqua (King, 1832). For several species, the oldest occurrences and range extensions are reported. Co-occurrence of warm water taxa, previously assigned to MIS 11, and typical Pliocene taxa on Mejillones cannot be confirmed. Pliocene and Pleistocene mollusk faunas from Mejillones are listed for comparison. 相似文献
226.
Edita Karosiene Michael Rasmussen Thomas Blicher Ole Lund Søren Buus Morten Nielsen 《Immunogenetics》2013,65(10):711-724
Major histocompatibility complex class II (MHCII) molecules play an important role in cell-mediated immunity. They present specific peptides derived from endosomal proteins for recognition by T helper cells. The identification of peptides that bind to MHCII molecules is therefore of great importance for understanding the nature of immune responses and identifying T cell epitopes for the design of new vaccines and immunotherapies. Given the large number of MHC variants, and the costly experimental procedures needed to evaluate individual peptide–MHC interactions, computational predictions have become particularly attractive as first-line methods in epitope discovery. However, only a few so-called pan-specific prediction methods capable of predicting binding to any MHC molecule with known protein sequence are currently available, and all of them are limited to HLA-DR. Here, we present the first pan-specific method capable of predicting peptide binding to any HLA class II molecule with a defined protein sequence. The method employs a strategy common for HLA-DR, HLA-DP and HLA-DQ molecules to define the peptide-binding MHC environment in terms of a pseudo sequence. This strategy allows the inclusion of new molecules even from other species. The method was evaluated in several benchmarks and demonstrates a significant improvement over molecule-specific methods as well as the ability to predict peptide binding of previously uncharacterised MHCII molecules. To the best of our knowledge, the NetMHCIIpan-3.0 method is the first pan-specific predictor covering all HLA class II molecules with known sequences including HLA-DR, HLA-DP, and HLA-DQ. The NetMHCpan-3.0 method is available at http://www.cbs.dtu.dk/services/NetMHCIIpan-3.0. 相似文献
227.
228.
229.
Kasper Worm-Leonhard Thomas Hjelmgaard Rasmus K. Petersen Karsten Kristiansen John Nielsen 《Bioorganic & medicinal chemistry letters》2013,23(14):4162-4165
In this study we present the design, synthesis and biological evaluation of a small, first-generation library of small molecule aromatic amides based on the arylopeptoid skeleton. The compounds were efficiently synthesized using a highly convenient submonomer solid-phase methodology which potentially allows for access to great product diversity. The synthesized compounds were tested for their ability to activate peroxisome proliferator-activated receptors (PPARs) and they all acted as PPARγ agonists in the μM range spanning from 2.5- to 14.7-fold activation of the receptor. This is the first discovery of bioactive molecules based on the arylopeptoid architecture. 相似文献
230.
The fact that membrane proteins are notoriously difficult to analyse using standard protocols for atomic-resolution structure determination methods have motivated adaptation of these techniques to membrane protein studies as well as development of new technologies. With this motivation, liquid-state nuclear magnetic resonance (NMR) has recently been used with success for studies of peptides and membrane proteins in detergent micelles, and solid-state NMR has undergone a tremendous evolution towards characterization of membrane proteins in native membrane and oriented phospholipid bilayers. In this mini-review, we describe some of the technological challenges behind these efforts and provide examples on their use in membrane biology. 相似文献