全文获取类型
收费全文 | 2049篇 |
免费 | 31篇 |
国内免费 | 25篇 |
出版年
2023年 | 5篇 |
2022年 | 6篇 |
2021年 | 20篇 |
2020年 | 26篇 |
2019年 | 21篇 |
2018年 | 45篇 |
2017年 | 33篇 |
2016年 | 31篇 |
2015年 | 48篇 |
2014年 | 110篇 |
2013年 | 141篇 |
2012年 | 130篇 |
2011年 | 159篇 |
2010年 | 120篇 |
2009年 | 115篇 |
2008年 | 102篇 |
2007年 | 107篇 |
2006年 | 102篇 |
2005年 | 89篇 |
2004年 | 83篇 |
2003年 | 52篇 |
2002年 | 36篇 |
2001年 | 19篇 |
2000年 | 28篇 |
1999年 | 28篇 |
1998年 | 21篇 |
1997年 | 34篇 |
1996年 | 49篇 |
1995年 | 47篇 |
1994年 | 27篇 |
1993年 | 21篇 |
1992年 | 19篇 |
1991年 | 23篇 |
1990年 | 14篇 |
1989年 | 12篇 |
1988年 | 11篇 |
1987年 | 12篇 |
1986年 | 13篇 |
1985年 | 27篇 |
1984年 | 32篇 |
1983年 | 21篇 |
1982年 | 26篇 |
1981年 | 13篇 |
1980年 | 13篇 |
1979年 | 4篇 |
1978年 | 4篇 |
1977年 | 2篇 |
1974年 | 3篇 |
1973年 | 1篇 |
排序方式: 共有2105条查询结果,搜索用时 26 毫秒
41.
Gudrun Ljunger Patrick Adlercreutz Bo Mattiasson 《Biocatalysis and Biotransformation》1993,7(4):279-288
-Chymotrypsin was modified with cyanuric chloride activated monomethoxypolyethylene glycol (MPEG) with molecular weights 1900 and 5000. Using the higher molecular weight MPEG a product that was soluble in benzene at moderate levels of modification was obtained, whereas with MPEG 1900 almost all the enzyme's amino groups had to be modified for dissolving the conjugate. The catalytic activity decreased with increasing degree of substitution. Apparent Vmax was considerably higher for the less modified enzyme preparation than for the more modified one, while Km,app stayed almost constant. The modified enzyme was used for peptide synthesis. The reaction was dependent on the content of dissolved water. Both Vmax,app and Km,app increased with increasing water content. It was possible to achieve a process with complete conversion of substrate to dipeptide. 相似文献
42.
通过对寡肽N-末端α-羰酰及喹喔啉衍生物和荧光在碘化钾、乙二醇、盐酸胍和氯化钠溶液中的变化测定结果表明:不同一级结构寡肽的羰酰荧光物的碘化钾淬灭过程彼此有差异.在不同浓度的乙二醇和盐酸胍溶液中,第三位氨基酸残基的种类和构型不同的寡肽羰酰衍生物的荧光变化亦有不同.乙二醇引起羰酰甘氨寡肽荧先发射峰位红移.丙氨寡肽的发射峰位蓝移;并且不同链长的甘氨短肽及丙氨短肽羰酰衍生物在不同浓度的乙二醇或盐酸胍溶液中各自的荧光变化有差异,但这种差异随肽链的延长逐渐减小.以上结果提示:尽管(含有2-6个氨基酸残基的)寡肽在溶液中难以形成二级结构,但它们的空间构象可能不是随机的;寡肽链越长,结构相对稳定. 相似文献
43.
通过对寡肽N-末端α-羰酰及喹喔啉衍生物和荧光在碘化钾、乙二醇、盐酸胍和氯化钠溶液中的变化测定结果表明:不同一级结构寡肽的羰酰荧光物的碘化钾淬灭过程彼此有差异.在不同浓度的乙二醇和盐酸胍溶液中,第三位氨基酸残基的种类和构型不同的寡肽羰酰衍生物的荧光变化亦有不同.乙二醇引起羰酰甘氨寡肽荧先发射峰位红移.丙氨寡肽的发射峰位蓝移;并且不同链长的甘氨短肽及丙氨短肽羰酰衍生物在不同浓度的乙二醇或盐酸胍溶液中各自的荧光变化有差异,但这种差异随肽链的延长逐渐减小.以上结果提示:尽管(含有2-6个氨基酸残基的)寡肽在溶液中难以形成二级结构,但它们的空间构象可能不是随机的;寡肽链越长,结构相对稳定. 相似文献
44.
Gaetano Barbato Daniel O. Cicero Elisabetta Bianchi Antonello Pessi Renzo Bazzo 《Journal of biomolecular NMR》1996,8(1):36-48
Summary We describe the high-resolution structure by NMR of two peptides that belong to a combinatorial library based on the zinc-finger motif. The library represents, to the best of our knowledge, the first example of a conformationally homogeneous peptide library and was obtained by introducing random residues in five positions of the -helical portion of a 26-residue consensus peptide (CP1) belonging to the Cys2-Hys2 zinc-finger family. The result was shown to be a highly homogeneous -helical library (Bianchi et al., 1995). The structures of the parent compound (CP1) and of a representative member (CP1m) that was selected by screening the library with a monoclonal antibody are compared in detail as an example of the very high stability of the zinc-finger scaffold upon sequence variability. The two peptides exhibit an extremely high degree of structural similarity. The use of this type of conformationally constrained combinatorial library might represent a step forward in the design of peptidomimetics, as it considerably accelerates the process of the identification of the spatial relationship among the pharmacophoric groups.Abbreviations
t-Bu
tert-butyloxycarbonyl
- Fmoc
9-fluorenylmethoxycarbonyl 相似文献
45.
Summary Using a combinatorial peptide library method, we identified YIYGSFK as an efficient and specific peptide substrate for pp60c-src protein tyrosine kinase (PTK) [Lam et al., Int. J. Pept. Protein Res., 45 (1995) 587]. Employing YIYGSFK as a template, we synthesized and evaluated a series of pseudosubstrate-based inhibitors for pp60c-src. We found that the efficiency of a given inhibitor was highly dependent on the specific tyrosine analog used at the phosphorylation site of the substrate. One of these pseudosubstrate inhibitors, YI(2-Nal)GSFK, selectively inhibited the kinase activity of pp60c-src, with a Ki of 24 M. This peptide inhibitor exhibited selectivity for pp60c-src as compared to other PTKs tested, such as c-Abl and Bcr-Abl. Our results suggest that selective inhibitors for a specific PTK can be developed when the structure of a specific and efficient small peptide substrate for this PTK can be used as a template for structure modification.Abbreviations 1-Nal
l-1-naphthylalanine
- 2-Nal
l-2-naphthylalanine
- BOP
benzotriazolyl-N-oxy-tris(dimethylamino)-phosphonium hexafluorophosphate
- BSA
bovine serum albumin
- cAPK
cyclic AMP-dependent protein kinase
- DIEA
diisopropylethylamine
- EGFR
epidermal growth factor receptor
- Fmoc
fluorenylmethoxycarbonyl
- HOBt
1-hydroxybenzotriazole
- MES
2-[N-morpholino]ethanesulfonic acid
- PBS
phosphate-buffered salts
- pCl
l-p-chlorophenylalanine
- pF
l-p-fluorophenylalanine
- PTK
protein tyrosine kinase
- TLC
thin-layer chromatography 相似文献
46.
Cynthia G. Fields Beate Grab Janelle L. Lauer Andrew J. Miles Ying-Ching Yu Gregg B. Fields 《Letters in Peptide Science》1996,3(1):3-16
Summary The triple-helical conformation of collagen has been proposed to be important for mediation of cellular activities, such as adhesion and activation, extracellular matrix assembly, and enzyme function. We have developed synthetic protocols that allow for the study of biological activities of specific collagen sequences in triple-helical conformation. These methods primarily involve solid-phase assembly and covalent linkage of three peptide chains. The resultant triple-helical peptides have sufficient thermal stabilities to permit structural and biological characterization under physiological conditions. The present article critically reviews the various approaches for constructing synthetic triple-helices.This paper is based on a presentation given at the Symposium on Peptide Structure and Design as part of the 31st Annual ACS Western Regional Meeting held in San Diego, CA, USA, October 18–21, 1995. 相似文献
47.
Summary We have found that guanidine acetate catalyses the transformation of a -benzyl-aspartyl peptide (Boc-Asp-(OBzl)-Leu-Trp-OMe) to an aminosuccinyl peptide (Boc-Asu-Leu-Trp-OMe). The reaction was accompanied by partial epimerization. However, not even a small amount of epimerization could be detected when the aminosuccinyl peptide was synthesised from Boc-Asp-Leu-Trp-OMe with the addition of DIC, HOPfp and guanidine acetate (as a catalyst). This reaction seems to be suitable for the epimerization-free solid phase synthesis of aminosuccinyl peptides, e.g. Asu6-Lamprey-III-GnRH (Glp-His-Trp-Ser-His-Asu-Trp-Lys-Pro-Gly-NH2). 相似文献
48.
Glenn L. Millhauser Chris J. Stenland Kimberly A. Bolin Frank J. M. van de Ven 《Journal of biomolecular NMR》1996,7(4):331-334
Summary Alanine-rich peptides serve as models for exploring the factors that control helix structure in peptides and proteins. Scalar CH-NH couplings (3JHN) are an extremely useful measure of local helix content; however, the large alanine content in these peptides leads to significant signal overlap in the CH region of 1H 2D NMR spectra. Quantitative determination of all possible 3JHN values is, therefore, very challenging. Szyperski and co-workers [(1992) J. Magn. Reson., 99, 552–560] have recently developed a method for determining 3JHN from NOESY spectra. Because 3JHN may be determined from 2D peaks outside of the CH region, there is a much greater likelihood of identifying resolved resonances and measuring the associated coupling constants. It is demonstrated here that 3JHN can be obtained for every residue in the helical peptide Ac-(AAAAK)3A-NH2. The resulting 3JHN profile clearly identifies a helical structure in the middle of the peptide and further suggests that the respective helix termini unfold via distinct pathways.Abbreviations
3JHN
three-bond CH-NH scalar coupling constant
- NOE
nuclear Overhauser enhancement
- NOESY
two-dimensional nuclear Overhauser spectroscopy
- COSY
two-dimensional correlated spectroscopy
- DQF-COSY
two-dimensional double-quantum-filtered correlated spectroscopy
- TOCSY
two-dimensional total correlation spectroscopy
To whom correspondence should be addressed.Deceased March 5, 1996. 相似文献
49.
Dimitri Coucouvanis 《Journal of biological inorganic chemistry》1996,1(6):594-600
Reactivity studies of clusters that contain the MFe3S4 cores (M = Mo, V) with catecholate, multicarboxylate (or DMF) ligands coordinated to the Mo (or V) atoms, and Cl ligands
coordinated to the Fe atoms have been carried out. These studies show the M/Fe/S single cubane clusters to be effective catalysts
in the reduction of nitrogenase substrates such as hydrazine, acetylene and protons to give ammonia, ethylene and dihydrogen
respectively. The same molecules do not activate or catalyze the reduction of dinitrogen. The results indicate that the observed
catalyses are occurring at the Mo (V) sites by a process that, in the case of hydrazine, involves substrate protonation prior
to reduction. The facile catalytic reduction of hydrazine by clusters that contain coordinatively saturated polycarboxylate-bound
Mo atoms is rationalized in terms of a possible protonation/proton delivery function of the coordinated polycarboxylate ligands.
The reactivity characteristics of the M/Fe/S clusters (structurally quite similar to the nitrogenase cofactor) have led to
the suggestion that the Mo (V) atoms may be involved in the reduction of hydrazine in the later stages of dinitrogen reduction.
Received and accepted: 21 August 1996 相似文献
50.
Bruno Eto Michel Boisset Peter Eden Ambikaipakan Balasubramaniam Jehan-Franois Desjeux 《Peptides》1995,16(8):1403-1409
The aim of our study was to determine whether a meal modifies the antisecretory response induced by PYY and the structural requirements to elicit antisecretory effects of analogue PYY(22–36) for potential antidiarrhea therapy. The variations in short-circuit current (Isc) due to the modification of ionic transport across the rat intestine were assessed in vitro, using Ussing chambers. In fasted rats, PYY induced a dose- and time-dependent reduction in Isc, with a sensitivity threshold at 5 × 10−11 M (ΔIsc −2 ± 0.5 μA/cm2). The reduction was maximal at 10−7 M (Isc −23 ± 2 μA/cm2), and the concentration producing half-maximal inhibition was 10−9 M. At 10−7 M, reduction of Isc by PYY reached 90% of response to 5 × 10−5 M bumetanide. The PYY effect was partly reversed by 10−5 M forskolin (Isc +13.43 ± 2.91 μA/h·cm2, p < 0.05) or 10−3 M dibutyryl adenosine 3′,5′ cyclic monophosphate (Isc +12 ± 1.69 μA/cm2, p < 0.05). Naloxone and tetrodotoxin did not alter the effect of PYY. In addition, PYY and its analogue P915 reduced net chloride ion secretion to 2.85 and 2.29 μEq/cm2 (p < 0.05), respectively. The antisecretory effect of PYY was accompanied by dose- and time-dependent desensitization when jejunum was prestimulated by a lower dose of peptide. The antisecretory potencies exhibited by PYY analogues required both a C-terminal fragment (22–36) and an aromatic amino acid residue (Trp or Phe) at position 27. At 10−7 M the biological activity of PYY was lower in fed than fasted rats (p < 0.001). Our results confirm the antisecretory effect of PYY, but show that the fed period is accompanied by desensitization, similar to the transient desensitization observed in the fasted period with cumulative doses. This suggests that PYY may act as a physiological mediator that reduces intestinal secretion. 相似文献