全文获取类型
收费全文 | 651篇 |
免费 | 57篇 |
专业分类
708篇 |
出版年
2023年 | 3篇 |
2022年 | 3篇 |
2021年 | 10篇 |
2020年 | 7篇 |
2019年 | 9篇 |
2018年 | 19篇 |
2017年 | 10篇 |
2016年 | 20篇 |
2015年 | 29篇 |
2014年 | 32篇 |
2013年 | 33篇 |
2012年 | 36篇 |
2011年 | 29篇 |
2010年 | 28篇 |
2009年 | 11篇 |
2008年 | 22篇 |
2007年 | 27篇 |
2006年 | 22篇 |
2005年 | 21篇 |
2004年 | 24篇 |
2003年 | 24篇 |
2002年 | 21篇 |
2001年 | 21篇 |
2000年 | 15篇 |
1999年 | 22篇 |
1998年 | 6篇 |
1997年 | 9篇 |
1996年 | 6篇 |
1995年 | 4篇 |
1994年 | 9篇 |
1993年 | 4篇 |
1992年 | 10篇 |
1991年 | 8篇 |
1990年 | 9篇 |
1989年 | 10篇 |
1988年 | 10篇 |
1987年 | 16篇 |
1986年 | 8篇 |
1985年 | 11篇 |
1984年 | 4篇 |
1983年 | 5篇 |
1982年 | 6篇 |
1977年 | 5篇 |
1975年 | 6篇 |
1974年 | 8篇 |
1973年 | 3篇 |
1972年 | 5篇 |
1971年 | 4篇 |
1970年 | 6篇 |
1969年 | 4篇 |
排序方式: 共有708条查询结果,搜索用时 0 毫秒
11.
Marianna F. Asaroa Andreas Mayr Bart Kahra Donna Van Engen 《Inorganica chimica acta》1994,220(1-2):335-346
Reaction of the allylidene tungsten complex [W(CPhCHCHMe)Br2(CO)2(4-picoline)] (1) with the dithiocarbamates MS2CNR2 (a: M=Na, R=Et; b: M=Na, R=Me; c: M=Li, R=Ph) in THF at 50 °C affords the vinylketene tungsten complexes [W(S2CNR2)2(OCCPhCHCHMe)(CO)] (2a–c). At lower temperatures, four reaction intermediates (3–6) may be discerned. Spectroscopic studies indicate that these compounds contain η4-allyldithiocarbamate ligands which are generated by addition of dithiocarbamate across the metal-carbon double bond of the allylidene-tungsten unit in 1. The structures of [W(S2CNEt2)2(OCCPhCHCHMe)(CO)] (2a) and of one intermediate, [W(η4-Et2NCS2CPhCHCHMe)(S2CNEt2)(CO)2] (5a) were elucidated by X-ray crystallography. 相似文献
12.
Role of the Cys 2-Cys 10 disulfide bond for the structure, stability, and folding kinetics of ribonuclease T1. 总被引:2,自引:0,他引:2 下载免费PDF全文
L. M. Mayr D. Willbold O. Landt F. X. Schmid 《Protein science : a publication of the Protein Society》1994,3(2):227-239
The Cys 2-Cys 10 disulfide bond in ribonuclease T1 was broken by substituting Cys 2 and Cys 10 by Ser and Asn, respectively, as present in ribonuclease F1. This C2S/C10N variant resembles the wild-type protein in structure and in catalytic activity. Minor structural changes were observed by 2-dimensional NMR in the local environment of the substituted amino acids only. The thermodynamic stability of ribonuclease T1 is strongly reduced by breaking the Cys 2-Cys 10 bond, and the free energy of denaturation is decreased by about 10 kJ/mol. The folding mechanism is not affected, and the trans to cis isomerizations of Pro 39 and Pro 55 are still the rate-limiting steps of the folding process. The differences in the time courses of unfolding and refolding are correlated with the decrease in stability: the folding kinetics of the wild-type protein and the C2S/C10N variant become indistinguishable when they are compared under conditions of identical stability. Apparently, the Cys 2-Cys 10 disulfide bond is important for the stability but not for the folding mechanism of ribonuclease T1. The breaking of this bond has the same effect on stability and folding kinetics as adding 1 M guanidinium chloride to the wild-type protein. 相似文献
13.
14.
Homogeneity-time is defined and introduced as the criterion for mixing quality in bioreactors. The criterion could replace the mixing time, in the case, when more than one measuring point (sensors) is included in the measuring system. Results based on the homogeneity-time and the temperature pulse method, achieved in stirred tank reactors under aerated conditions as well as in a jet-mixed tank, are presented.List of Symbols
C
p,p
kJ/kg K
Heat capacity of the pulse medium
-
C
p,s
kJ/kg K
Heat capacity of the reactor-medium
-
F m3/s
Flow rate of the pulse-input
-
i
Inhomogeneity
-
I
N
Inhomogeneity-number
-
M (t) °C
Ideal response curve
-
m
deNumber of combinations for certain number of sensors acc. to Table 1
-
n
Number of sensor
-
p
kg/m3
Density of the pulse medium
-
kg/m3
Density of the tank medium
-
s
1
°C
Mean absolute deviation of the sensor temperatures related on the ideal response curve s2 s Mean absolute deviation of the homogeneity-times related on the time achieved with 6 sensors
-
t s
Time
-
t (i) s
Homogeneity-time
-
t
ps
s
Starting time of tracer injection
-
t
PE
s
End time of tracer injection
-
T
E
°C
Mean medium temperature at the end of experiment
-
T
k
°C
Temperature at k-th sensor position
-
T
p
°C
Pulse temperature
-
T
s
°C
Mean medium temperature before the tracer injection
-
V
s
m3
Tank volume before pulse input 相似文献
15.
We present a general model for the evolution of chromosome-specific satellite DNA subfamilies.Sus scrofa domestica has a bimodal karyotype with two autosomal subsets of 12 meta-/submetacentric (Mc) and 6 acrocentric (Ac) chromosome types (Mc and Ac subgenomes). We show that the centromeric heterochromatin is characterised by two distinct satellite DNA families designed Mc1 and Ac2. Mc1 is a diverse satellite family of the Mc subgenome of which certain members with a 100 bp repeat unit are found to occur at the pericentromeric regions of each Mc autosome, while others are chromosome-specific, e.g. clone Mc pAv1.5, a higher order repeat variant, which hybridises specifically to chromosome 1. Ac2 is a homogeneous satellite occurring at the subterminal pericentromeric regions of all Ac autosomes. DNA sequence analyses showed that all clones investigated are built up from a 14 bp repeat unit which is highly conserved. In situ hybridisation to meiotic pachytene nuclei revealed a distinct spatial arrangement of the Ac2 centromeric satellite. 相似文献
16.
Characterization of the calmodulin-binding sites of muscle phosphofructokinase and comparison with known calmodulin-binding domains 总被引:7,自引:0,他引:7
Calmodulin has been shown to interact with high affinity with muscle phosphofructokinase (Mayr, G. W. (1984) Eur. J. Biochem. 143, 513-520, 521-529). In this study, direct binding measurements indicated that each of the two subunits of dimeric phosphofructokinase bound two calmodulins with Kd values of about 3 nM and 1 microM, respectively, in a strictly Ca2+-dependent way. To get more detailed information about this interaction, calmodulin-binding fragments were isolated from a CNBr digest of phosphofructokinase using affinity chromatography on calmodulin-agarose. Two fragments, M11 (Mr 3080) and M22 (Mr 8060), formed a 1:1 stoichiometric complex with Ca2+-calmodulin. The amino acid sequences of these fragments were determined, and their positions in the three-dimensional structure-model of phosphofructokinase are proposed. Fragment M11, which binds to calmodulin with the higher affinity (Kd 11.4 nM), is located in a region of the subunit where two dimers have been proposed to make contacts if associating to active tetrameric enzyme. A stabilization of the dimeric form of the enzyme by binding of calmodulin supports this location of M11. The weaker binding fragment M22 (Kd 198 nM) corresponds to the C-terminal part of the polypeptide and contains the site which is phosphorylated by cAMP-dependent protein kinase. Both fragments have structural properties in common with the isolated calmodulin-binding domains of myosin light chain kinase: two cationic segments rich in hydrophobic residues, one constantly possessing a tryptophan, and the other exhibiting an amino acid sequence resembling sites phosphorylated by cAMP-dependent protein kinase. 相似文献
17.
Synthesis and application of photoaffinity analogues of inositol 1,4,5-trisphosphate selectively substituted at the 1-phosphate group. 下载免费PDF全文
R Sch?fer M Nehls-Sahabandu B Grabowsky M Dehlinger-Kremer I Schulz G W Mayr 《The Biochemical journal》1990,272(3):817-825
We have synthesized two photolabile arylazido-analogues of Ins(1,4,5)P3 selectively substituted at the 1-phosphate group for determination of Ins(1,4,5)P3-binding proteins. These two photoaffinity derivatives, namely N-(4-azidobenzoyl)aminoethanol-1-phospho-D-myo-inositol 4,5-bisphosphate (AbaIP3) and N-(4-azidosalicyl)aminoethanol-1-phospho-D-myo-inositol 4,5-bisphosphate (AsaIP3), bind to high affinity Ins(1,4,5)P3-specific binding sites at a 9-fold lower affinity (Kd = 66 and 70 nM) than Ins(1,4,5)P3 (Kd = 7.15 nM) in a fraction from rat pancreatic acinar cells enriched in endoplasmic reticulum (ER). Other inositol phosphates tested showed comparable (DL-myo-inositol 1,4,5-trisphosphothioate, Kd = 81 nM) or much lower affinities for the binding sites [Ins(1,3,4,5)P4, Kd = 4 microM; Ins(1,4)P2, Kd = 80 microM]. Binding of AbaIP3 was also tested on a microsomal preparation of rat cerebellum [Kd = 300 nM as compared with Ins(1,4,5)P3, Kd = 45 nM]. Ca2+ release activity of the inositol derivatives was tested with AbaIP3. It induced a rapid and concentration-dependent Ca2+ release from the ER fraction [EC50 (dose producing half-maximal effect) = 3.1 microM] being only 10-fold less potent than Ins(1,4,5)P3 (EC50 = 0.3 microM). From the two radioactive labelled analogues ([3H]AbaIP3 and 125I-AsIP3) synthesized, the radioiodinated derivative was used for photoaffinity labelling. It specifically labelled three proteins with apparent molecular masses of 49, 37 and 31 kDa in the ER-enriched fraction. By subfractionation of this ER-enriched fraction on a Percoll gradient the 37 kDa Ins(1,4,5)P3 binding protein was obtained in a membrane fraction which showed the highest effect in Ins(1,4,5)P3-inducible Ca2+ release (fraction P1). The other two Ins(1,4,5)P3-binding proteins, of 49 and 31 kDa, were obtained in fraction P2, in which Ins(1,4,5)P3-induced Ca2+ release was half of that obtained in fraction P1. We conclude from these data that the 37 kDa and/or the 49 and 31 kDa proteins are involved in Ins(1,4,5)P3-induced Ca2+ release from the ER of rat pancreatic acinar cells. 相似文献
18.
The refined 2.15 A X-ray crystal structure of human liver cathepsin B: the structural basis for its specificity. 总被引:8,自引:3,他引:8 下载免费PDF全文
D Musil D Zucic D Turk R A Engh I Mayr R Huber T Popovic V Turk T Towatari N Katunuma et al. 《The EMBO journal》1991,10(9):2321-2330
From the lysosomal cysteine proteinase cathepsin B, isolated from human liver in its two-chain form, monoclinic crystals were obtained which contain two molecules per asymmetric unit. The molecular structure was solved by a combination of Patterson search and heavy atom replacement methods (simultaneously with rat cathepsin B) and refined to a crystallographic R value of 0.164 using X-ray data to 2.15 A resolution. The overall folding pattern of cathepsin B and the arrangement of the active site residues are similar to the related cysteine proteinases papain, actinidin and calotropin DI. 166 alpha-carbon atoms out of 248 defined cathepsin B residues are topologically equivalent (with an r.m.s. deviation of 1.04 A) with alpha-carbon atoms of papain. However, several large insertion loops are accommodated on the molecular surface and modify its properties. The disulphide connectivities recently determined for bovine cathepsin B by chemical means were shown to be correct. Some of the primed subsites are occluded by a novel insertion loop, which seems to favour binding of peptide substrates with two residues carboxy-terminal to the scissile peptide bond; two histidine residues (His110 and His111) in this "occluding loop' provide positively charged anchors for the C-terminal carboxylate group of such polypeptide substrates. These structural features explain the well-known dipeptidyl carboxypeptidase activity of cathepsin B. The other subsites adjacent to the reactive site Cys29 are relatively similar to papain; Glu245 in the S2 subsite favours basic P2-side chains. The above mentioned histidine residues, but also the buried Glu171 might represent the group with a pKa of approximately 5.5 near the active site, which governs endo- and exopeptidase activity. The "occluding loop' does not allow cystatin-like protein inhibitors to bind to cathepsin B as they do to papain, consistent with the reduced affinity of these protein inhibitors for cathepsin B compared with the related plant enzymes. 相似文献
19.
20.
Sequential staining with a counterstain-contrasted fluorescent R-banding technique (chromomycin A3/distamycin A-DAPI) followed by DAPI-actinomycin D-induced quinacrine-fluorescence-Hoechst 33258 (QFH)-type banding allowed the identification of quail chromosomes up to chromosome 19. The chromomycin A3-positive staining behavior of the W chromosome and of the heterochromatic areas of most microchromosomes indicated their GC-rich nature. 相似文献