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21.
Amanda Rui En Woo Siu Kwan Sze Hwa Hwa Chung Valerie C-L Lin 《Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms》2019,1862(4):522-533
The activation functions AF1 and AF2 of nuclear receptors mediate the recruitment of coregulators in gene regulation. AF1 is mapped to the highly variable and intrinsically unstructured N terminal domain and AF2 lies in the conserved ligand binding domain. The unstructured nature of AF1 offers structural plasticity and hence functional versatility in gene regulation. However, little is known about the key functional residues of AF1 that mediates its interaction with coregulators. This study focuses on the progesterone receptor (PR) and reports the identification of K464, K481 and R492 (KKR) as the key functional residues of PR AF1. The KKR are monomethylated and function cooperatively. The combined mutations of KKR to QQQ render PR isoform B (PRB) hyperactive, whereas KKR to FFF mutations abolishes as much as 80% of PR activity. Furthermore, the hyperactive QQQ mutation rescues the loss of PR activity due to E911A mutation in AF2. The study also finds that the magnitudes of the mutational effect differ in different cell types as a result of differential effects on the functional interaction with coregulators. Furthermore, KKR provides the interface for AF1 to physically interact with p300 and SRC-1, and with AF2 at E911. Intriguingly, the inactive FFF mutant interacts strikingly stronger with both SRC-1 and AF2 than wt PRB. We propose a tripartite model to describe the dynamic interactions between AF1, AF2 and SRC-1 with KKR of AF1 and E911 of AF2 as the interface. An overly stable interaction would hamper the dynamics of disassembly of the receptor complex. 相似文献
22.
Bacterial sulfate reduction and salinity: two controls on dolomite precipitation in Lagoa Vermelha and Brejo do Espinho (Brazil) 总被引:1,自引:0,他引:1
Y. van Lith C. Vasconcelos R. Warthmann J.C.F. Martins J.A. McKenzie 《Hydrobiologia》2002,485(1-3):35-49
The hydrological system of Lagoa Vermelha, a dolomite-precipitating lagoon in Brazil, was investigated using hydrogen and oxygen stable isotopic composition of the water collected during an annual cycle (1996–1997). These data demonstrated that dolomite formed in May–June during high saline conditions. High salinity apparently provides the ions and saturation state necessary for dolomite precipitation. Ion concentrations in the lagoon water indicated an identical timing of dolomite precipitation and demonstrated that dolomite formed at decreased sulfate concentrations. In Brejo do Espinho, a neighbouring lagoon, the ion concentrations in the water column revealed that dolomite precipitates throughout the year, most likely due to its higher salinity than Lagoa Vermelha during the measured period. In Lagoa Vermelha, high 34S of pore water sulfate and high sulfide concentrations correlated with dolomitic horizons, demonstrating the association of bacterial sulfate reduction with dolomite formation. In Brejo do Espinho high 34S of pore water sulfate and high sulfide concentrations occurred throughout the dolomitic sedimentary column. We conclude that elevated salinity and sulfate reduction are the main factors inducing dolomite precipitation in these lagoons, confirming the microbial dolomite formation theory. These results suggest that there may be other settings where sulfate-reducing bacteria induce dolomite precipitation under saline conditions, such as deep-sea sediments or sabkhas, and imply that microbial dolomite may significantly contribute to the sedimentary carbonate budget, particularly in the earliest Earth's history when anoxic conditions were more prevalent. 相似文献
23.
白细胞介素2亲和性配体的筛选 总被引:3,自引:0,他引:3
白细胞介素2(IL-2)及其受体拮抗剂的研究对免疫抑制药物的研制具有重要作用.抗白细胞介素2受体α链中和性单克隆抗体5G1(抗Tac型抗体)能够特异性地阻断IL-2与其受体的结合.因此,5G1可作为目标分子被用来在噬菌体展示肽库中筛选白细胞介素2的亲和性配体.经过4轮亲和性筛选以及5G1亲和活性的测定,6个具有明显5G1亲和活性的噬菌体克隆被发现.DNA序列分析结果显示出,所得到的肽序列具有明显的保守性,即SSFT(L/P)I.该序列与IL-2受体α链没有同源性.因此,SSFT(L/P)I可能模拟了IL-2受体α链上的一个不连续表位(mimotope),为白细胞介素2亲和性配体片段. 相似文献
24.
Calcimedins: purification and characterization from chicken gizzard and rat and bovine livers 总被引:2,自引:0,他引:2
A procedure for the simultaneous extraction and purification of four calcimedins from chicken gizzard, rat liver, and bovine liver is described. These proteins bind to hydrophobic resins in a calcium-dependent manner similar to calmodulin and troponin C. The four calcimedins purified had molecular weights 67,000 (67K), 35,000 (35K), 33,000 (33K), and 30,000 (30K) as determined by SDS polyacrylamide gel electrophoresis. Their ability to bind calcium was demonstrated using the Hummel-Dreyer method. Their tissue concentration ranged between 1-4 mg/100 g wet weight in the three tissues studied. During gel filtration, calcimedins 67K and 35K, had Rf (Ve-Vo/Vt-Vo) values of 0.46 and 0.74, respectively, indicating monomeric structure. However, the 33K and 30K calcimedins had Rf values of 0.26 (molecular weights greater than 90,000) suggesting that they occur as subunit complexes in their native state. Antibodies raised against the 67K and 35K calcimedins showed cross reactivity suggesting possible common origin. However, peptide mapping studies showed that they are independent proteins with considerable peptide homology. Antibodies to 30/33K calcimedins did not cross-react with either 67K or 35K calcimedins. Moreover, their peptide maps were strikingly different from those of 67K and 35K calcimedins indicating that they are unique. At present, the regulatory function of this group of proteins is not clear. Indirect evidences support the possibility that they are involved in membrane associated events, such as endocytosis and secretion. 相似文献
25.
Intact Transition Epitope Mapping – Targeted High-Energy Rupture of Extracted Epitopes (ITEM-THREE),
《Molecular & cellular proteomics : MCP》2019,18(8):1543-1555
Highlights
- •Multiplex epitope mapping/antigenic determinant identification in the gas phase.
- •Intact transition and controlled dissociation of immune complexes by MS.
- •Simultaneous identification and amino acid sequence determination of epitopes.
- •Simplified in-solution sample handling because of ion manipulation and filtering by MS.
26.
Caperna TJ Rosebrough RW McMurtry JP Vasilatos-Younken R 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》1999,124(4):541-421
We determined the effect of dietary protein on the distribution of insulin-like growth factor (IGF) binding proteins in chicken plasma. Three groups of male broilers (n=6 per group) were fed (ad libitum) isocaloric diets containing 12, 21 or 30% dietary protein. Birds were fed respective diets beginning at 7 days of age and killed at 28 days. No differences were observed between adequate (21%) and high (30%) protein intakes for any of the parameters investigated (growth criteria, plasma levels of IGF-I, growth hormone or IGF-binding proteins). Feeding protein deficient diets (12%) resulted in a 34% decrease in body weight, 17% decrease in feed intake and a 39% increase in feed/gain ratio. IGF-binding proteins in plasma samples were separated by SDS-PAGE and transferred to nitrocellulose sheets. Nitrocellulose blots were probed with [125I]chicken IGF-II. Four regions of binding activity corresponding to 70, 43, 30 and 24 kDa were observed in all samples. Birds consuming 12% dietary group protein had less than 50% of the 43-kDa binding activity of birds consuming 21 or 30% dietary protein. The 30-kDa binding activity was 42% lower in the 12% dietary protein group compared to birds consuming adequate protein. In contrast, 70- and 24-kDa binding activities were not influenced by dietary protein. Chickens consuming 12% dietary protein had higher levels of growth hormone and lower levels of IGF-I than those consuming 21 or 30% dietary protein. These data indicate that in chickens, the circulating levels of at least two independent IGF-binding proteins are influenced by dietary protein. 相似文献
27.
Silvia Gosiewska Anthony L. Spek Robertus J.M. Klein Gebbink 《Inorganica chimica acta》2007,360(1):405-417
Mononuclear iron(II) complexes of enantiopure Py(ProOH)2 (2) and Py(ProPh2OH)2 (3) ligands have been prepared with FeCl2 and Fe(OTf)2 · 2MeCN. Both ligands coordinate to the metal in a pentadentate fashion. Next to the meridional N,N′,N-coordination of the ligand, additional coordination of the oxygen atoms of both hydroxyl groups to the metal is found in complexes 4-7. Complex [FeCl(2)](Cl) (4) shows an octahedral geometry as determined by X-ray diffraction and is formed as a single diastereoisomer. The solution structures of complexes 4-7 were characterized by means of UV-Vis, IR, ESI-MS, conductivity and CD measurements. The catalytic potential of these complexes in the oxidation of alkenes and sulfides in the presence of H2O2 is presented. 相似文献
28.
Actin is a highly conserved protein although many isoforms exist. In vertebrates and insects the different actin isoforms
can be grouped by their amino acid sequence and tissue-specific gene expression into muscle and nonmuscle actins, suggesting
that the different actins may have a functional significance. We ask here whether atomic models for G- and F-actins may help
to explain this functional diversity. Using a molecular graphics program we have mapped the few amino acids that differ between
isoactins. A small number of residues specific for muscle actins are buried in internal positions and some present a remarkable
organization. Within the molecule, the replacements observed between muscle and nonmuscle actins are often accompanied by
compensatory changes. The others are dispersed on the protein surface, except for a cluster located at the N-terminus which
protrudes outward. Only a few of these residues specific for muscle actins are present in known ligand binding sites except
the N-terminus, which has a sequence specific for each isoactin and is directly implicated in the binding to myosin. When
we simulated the replacements of side chains of residues specific for muscle actins to those specific for nonmuscle actins,
the N-terminus appears to be less compact and more flexible in nonmuscle actins. This would represent the first conformational
grounds for proposing that muscle and nonmuscle actins may be functionally distinguishable. The rest of the molecule is very
similar or identical in all the actins, except for a possible higher internal flexibility in muscle actins. We propose that
muscle actin genes have evolved from genes of nonmuscle actins by substitutions leading to some conformational changes in
the protruding N-terminus and the internal dynamics of the main body of the protein.
Received: 15 March 1996 / Accepted: 14 July 1996 相似文献
29.
Respiration in Saccharomyces cerevisiae is regulated by small proteins such as the respiratory supercomplex factors (Rcf). One of these factors (Rcf1) has been shown to interact with complexes III (cyt. bc1) and IV (cytochrome c oxidase, CytcO) of the respiratory chain and to modulate the activity of the latter. Here, we investigated the effect of deleting Rcf1 on the functionality of CytcO, purified using a protein C-tag on core subunit 1 (Cox1). Specifically, we measured the kinetics of ligand binding to the CytcO catalytic site, the O2-reduction activity and changes in light absorption spectra. We found that upon removal of Rcf1 a fraction of the CytcO is incorrectly assembled with structural changes at the catalytic site. The data indicate that Rcf1 modulates the assembly and activity of CytcO by shifting the equilibrium of structural sub-states toward the fully active, intact form. 相似文献
30.