全文获取类型
收费全文 | 769篇 |
免费 | 28篇 |
国内免费 | 12篇 |
专业分类
809篇 |
出版年
2023年 | 4篇 |
2022年 | 5篇 |
2021年 | 3篇 |
2020年 | 13篇 |
2019年 | 24篇 |
2018年 | 30篇 |
2017年 | 19篇 |
2016年 | 21篇 |
2015年 | 10篇 |
2014年 | 32篇 |
2013年 | 111篇 |
2012年 | 6篇 |
2011年 | 23篇 |
2010年 | 17篇 |
2009年 | 25篇 |
2008年 | 28篇 |
2007年 | 33篇 |
2006年 | 26篇 |
2005年 | 31篇 |
2004年 | 29篇 |
2003年 | 25篇 |
2002年 | 21篇 |
2001年 | 20篇 |
2000年 | 16篇 |
1999年 | 21篇 |
1998年 | 20篇 |
1997年 | 25篇 |
1996年 | 18篇 |
1995年 | 16篇 |
1994年 | 13篇 |
1993年 | 10篇 |
1992年 | 6篇 |
1991年 | 8篇 |
1990年 | 8篇 |
1989年 | 11篇 |
1988年 | 8篇 |
1987年 | 6篇 |
1986年 | 4篇 |
1985年 | 12篇 |
1984年 | 10篇 |
1983年 | 3篇 |
1982年 | 13篇 |
1981年 | 10篇 |
1980年 | 5篇 |
1979年 | 2篇 |
1977年 | 3篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有809条查询结果,搜索用时 15 毫秒
1.
John W. Wright Anita J. Bechtholt Shelley L. Chambers Joseph W. Harding 《Peptides》1996,17(8):1365-1371
The present investigation determined that native angiotensins II and III (ANG II and III) were equipotent as pressor agents when ICV infused in alert rats, whereas native angiotensin IV (ANG IV) was less potent. An analogue of each of these angiotensins was prepared with a hydroxyethylamine (HEA) amide bond replacement at the N-terminus, yielding additional resistance to degradation. These three angiotensin analogues, HEA-ANG II, HEA-ANG III, and HEA-ANG IV, were equivalent with respect to maximum elevation in pressor responses when ICV infused; and each evidenced significantly extended durations of effect compared with their respective native angiotensin. Comparing analogues, HEA-ANG II had a significantly longer effect compared with HEA-ANG III, and HEA-ANG IV, whereas the latter were equivalent. Pretreatment with the AT1 receptor subtype antagonist, Losartan (DuP753), blocked subsequent pressor responses to each of these analogues, suggesting that these responses were mediated by the AT1 receptor subtype. Pretreatment with the specific AT4 receptor subtype antagonist, Divalinal (HED 1291), failed to influence pressor responses induced by the subsequent infusion of these analogues. These results suggest an important role for Ang III, and perhaps ANG IV, in brain angiotensin pressor responses mediated by the AT1 receptor subtype. 相似文献
2.
Summary The activated dimonophosphate of 3-deoxyadenosine (cordycepin) undergoes oligomerization to produce a new family of pyrophosphate-linked oligomers in which the average repeating unit involves a nine-atom structural group. The presence of a poly(U) template increase the relative yields of higher oligomers, although the template-free reaction is itself extremely efficient.For the previous paper in this series see Schwartz et al. (1987) 相似文献
3.
A. Benayad D. Benamar N. Van Mau G. Page F. Heitz 《European biophysics journal : EBJ》1991,20(4):209-213
Three different gramicidin A analogues bearing acyl chains of various length on the ethanolamine moiety have been studied by investigating their single channel behaviour and their monolayer properties. It is shown that the single channel conductance does not depend on the substitution of the ethanolamine OH group and that the channel lifetime is roughly proportional to the length of the alkyl chain. The monolayer study indicates that acylation of gramicidin A produces compounds which have medium-dependent conformations. These acylated compounds are miscible with lipids, while GA is not, and the surface potential is not modified by the esterification of the alcohol group.
Offprint requests to: F. Heitz 相似文献
4.
Distamycin and netropsin are two oligopeptides which bind to DNA in a nonintercalative manner. Analogues of distamycin have
been synthesized and their binding with poly d(A-T) studied using ultraviolet absorption spectroscopy. Preliminary biological
activity tests on a gram positive bacteria using these analogues have also been carried out
Based on the lecture given by Dr. V. Sasisekharan at the Royal Society of Chemistry (Deccan Section) Bangalore, 26 June 1984. 相似文献
5.
Biochemical significance of enhanced activity of fluorinated 1,25-dihydroxyvitamin D3 in human cultured cell lines 总被引:1,自引:0,他引:1
Several human cancer cells possess receptors for 1,25-dihydroxyvitamin D3[1,25-(OH)2D3]. In these cells 1,25-(OH)2D3 has a biphasic concentration-dependent regulatory effect on cell replication and specifically induces its own metabolism. We have studied the effects on these parameters of the native hormone together with those of two analogues fluorinated at the 24-carbon and of 1,24R,25-trihydroxyvitamin D3[1,24R,25-(OH)3D3]. The difluorinated analogue 24,24-difluoro-1,25-(OH)2D3[24,24-F2-1,25-(OH)2D3] is an approximately fivefold more potent inhibitor of cellular replication than the native hormone, while 1,24R,25-(OH)3D3 is about fivefold less potent. This enhanced potency of the fluorinated analogue parallels its enhanced potency in in vivo studies of its effects on calcium and mineral metabolism. However, although the analogue retains replication stimulatory activity, it is clearly no more potent than the native hormone in this activity: 1,24R,25-(OH)3D3 has no significant stimulatory activity. Exposure of the cells to 1,25-(OH)2D3 at 0.05 nM for 6 h increases the subsequent conversion of labelled hormone to aqueous phase soluble compounds by 6.7-fold. None of the other compounds had a similar effect at this concentration. At 10 nM all 1-hydroxylated compounds increased aqueous phase radioactivity about equally (13 to 17-fold); this effect is still specific since 25-OH D3 had no such effect even at 10 nM. Studies on the effects of the fluorinated analogues upon receptor binding of hormone in cell cytosols and uptake of hormone by intact cells clearly demonstrate that the enhanced activity of these analogues is not due to higher receptor affinity or more rapid access to intracellular receptor.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
6.
Independently of their agonistic or antagonistic activity on different isolated tissue preparations, the kinin analogues investigated induce histamine release on rat peritoneal mast cells. The effectivity of most compounds is 10 to 100 times higher than that of bradykinin. Beside the positively charged amino acids, the elongation at the N-terminus with hydrophobic amino acids and the replacement of amino acids in the bradykinin sequence (especially at position 7) with aromatic residues is important for a high histamine-releasing activity. 相似文献
7.
The effect of structural changes in the N-terminal amino acid of AIV, with respect to AT4 receptor binding, was examined by competition with [125I]AIV in bovine adrenal membranes. Analogues with modifications of the first residue α-amino group possessed lower affinities than the primary amine-containing parent compound. Peptides with a residue 1 α-carbon in the d conformation exhibited poor affinity for the AT4 receptor. Modifications of the residue 1 R-group demonstrate that a straight chain aliphatic moiety containing four carbons is optimal for receptor-ligand binding, as evidenced by the extremely high affinity of [Nle1]AIV (Ki = 3.59±0.51 pM). Replacement of the 1–2 peptide bond of AIV with the methylene bond isostere Ψ (CH2-NH), increased the Ki approximately fivefold, indicating that the peptide bond may be replaced wihle maintaining relatively high-affinity receptor binding. 相似文献
8.
The effect of structural changes in the N-terminal amino acid of AIV, with respect to AT4 receptor binding, was examined by competition with [125I]AIV in bovine adrenal membranes. Analogues with modifications of the first residue -amino group possessed lower affinities than the primary amine-containing parent compound. Peptides with a residue 1 -carbon in the
conformation exhibited poor affinity for the AT4 receptor. Modifications of the residue 1 R-group demonstrate that a straight chain aliphatic moiety containing four carbons is optimal for receptor-ligand binding, as evidenced by the extremely high affinity of [Nle1]AIV (Ki = 3.59±0.51 pM). Replacement of the 1–2 peptide bond of AIV with the methylene bond isostere Ψ (CH2-NH), increased the Ki approximately fivefold, indicating that the peptide bond may be replaced wihle maintaining relatively high-affinity receptor binding. 相似文献
9.
Currently, considerable research activities are focussing on biochemical, physiological and pathological aspects of the creatine kinase (CK) — phosphorylcreatine (PCr) — creatine (Cr) system (for reviews see [1, 2]), but only little effort is directed towards a thorough investigation of Cr metabolism as a whole. However, a detailed knowledge of Cr metabolism is essential for a deeper understanding of bioenergetics in general and, for example, of the effects of muscular dystrophies, atrophies, CK deficiencies (e.g. in transgenic animals) or Cr analogues on the energy metabolism of the tissues involved. Therefore, the present article provides a short overview on the reactions and enzymes involved in Cr biosynthesis and degradation, on the organization and regulation of Cr metabolism within the body, as well as on the metabolic consequences of 3-guanidinopropionate (GPA) feeding which is known to induce a Cr deficiency in muscle. In addition, the phenotype of muscles depleted of Cr and PCr by GPA feeding is put into context with recent investigations on the muscle phenotype of gene knockout mice deficient in the cytosolic muscle-type M-CK.Abbreviations Cr
creatine
- Crn
creatinine
- PCr
phosphorylcreatine
- CK
creatine kinase
- M-CK
cytosolic muscle type CK isoenzyme
- Mi-CK
mitochondrial CK isoenzyme
- AGAT
L-arginine: glycine amidinotransferase
- GAMT
S-adenosylmethionine: guanidinoacetate methyltransferase
- Arg
arginine
- Met
methionine
- GPA
guanidinopropionate=-guanidinopropionate
- PGPA
phosphorylated GPA
- GBA
3-guanidinobutyrate=-guanidinobutyrate
- CPEO
chronic progressive external ophthalmoplegia 相似文献
10.
Graham J. Moore Renee C. Ganter John M. Matsoukas John Hondrelis George Agelis Klemoenis Barlos Scott Wilkinson John Sandall Patrick Fowler 《Journal of molecular recognition : JMR》1994,7(4):251-256
A triad of interacting group (TyrOH? His$ \underline\ominus$O2C) in angiotensin II (ANG II) has been postulated to create the tyrosinate anion pharmacophore (tyanophore) responsible for receptor activation/triggering (Biochim. Biophys. Acta 1991, 1065, 21). In the present study we investigated the effects on bioactivity of substituting the Tyr4 residue in [Sar1]ANG II with other anionic or electronegative amino acids, and with a number of aromatic amino acids lacking a hydroxyl group. [Sar1 Nva(δ-OH)4]ANG II, [Sar1 Nva(δ-OCH3)4]ANG II, [Sar1 Met4]ANG II, [Sar1 Gln4]ANG II, [Sar1 Glu4]ANG II and [Sar1 DL -Alg4]ANG II had agonist activities in the rat isolated uterus assay of 4, 3, 19, 10, > 0.1 and > 0.1%, respectively, of that of ANG II. [Sar1 Nal4]ANG II, [Sar1 Pal4]ANG II, [Sar1 DL -Phg(4′-F)4]ANG II, [Sar1 Phe(4′-F)4]ANG II, [Sar1 Phe(F5)4]ANG II and [Sar1 His4]ANG II had agonist activities of 4.5, 7, < 0.1, 0.2, 1 and 0.6%, respectively. All peptides investigated were devoid of measurable antagonist activity except [Sar1] Phe(4′-F)4 ANG II (pA2 = 7.7). These findings illustrate that anionic or electronegative aliphatic side chains replacing tyrosinate at position 4 can partially activate the angiotension receptor. For ANG II analogues containing an aromatic amino acid other than Tyr at position 4, ligand binding and agonist activity are not dependent on the electronegativity or dipole moment of the aromatic ring, or on the ability of the 4′ ring substituent to accept a proton. Modelling based on ab initio calculations of aromatic ring multipoles illustrate that the apparent binding affinity (PA2) of ANG II analogues is associated with a perpendicular electrostatic interaction of the position 4 aromatic ring with a receptor-based group. In addition, intramolecular interactions providing for the conformation of the ligand as it approaches its receptor appear to have a role in determining agonist vs antagonist activity. 相似文献