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11.
Structural analysis of the N- and C-termini in a peptide with consensus sequence. 总被引:3,自引:2,他引:1
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Y. Gong H. X. Zhou M. Guo N. R. Kallenbach 《Protein science : a publication of the Protein Society》1995,4(8):1446-1456
We present a structural analysis of a peptide, the sequence of which includes amino acids that show preferences for specific positions near the N- and C-termini in protein helices. This peptide has the sequence ac-YMSEDELKAAEAAFKRHGVP-amide, which includes a strong version of an N-terminal Harper-Rose capping box structure as well as a Gly located close to the C-terminus designed to elucidate its role in C-terminal capping. The sequence of five residues at the middle is inserted to separate effects at the two ends via a helix-stabilizing linker. Application of a simulated annealing procedure using interproton distance constraints derived from 1H NOESY experiments in water reveals the presence of a C-terminal structure in this model. The C-terminus forms a folded back structure in a significant fraction of structures generated by the annealing, in most of which Gly assumes an alpha L conformation. This structure occurs within a highly flexible region of the molecule and hence is occupied only a fraction of the time. 相似文献
12.
In the presence of Cl?, the severity of ammonia-induced inhibition of photosynthetic oxygen evolution is attenuated in spinach thylakoid membranes (Sandusky, P.O. and Yocum, C.F. (1983) FEBS Lett. 162, 339–343). A further examination of this phenomenon using steady-state kinetic analysis suggests that there are two sites of ammonia attack, only one of which is protected by the presence of Cl?. In the case of Tris-induced inhibition of oxygen evolution only the Cl? protected site is evident. In both cases the mechanism of Cl? protection involves the binding of Cl? in competition with the inhibitory amine. Anions (Br? and NO?3) known to reactive oxygen evolution in Cl?-depleted membranes also protect against Tris-induced inhibition, and reactivation of Cl?-depleted membranes by Cl? is competitively inhibited by ammonia. Inactivation of the oxygen-evolving complex by NH2OH is impeded by Cl?, whereas Cl? does not affect the inhibition induced by so-called ADRY reagents. We propose that Cl? functions in the oxygen-evolving complex as a ligand bridging manganese atoms to mediate electron transfer. This model accounts both for the well known Cl? requirement of oxygen evolution, and for the inhibitory effects of amines on this reaction. 相似文献
13.
14.
《MABS-AUSTIN》2013,5(5):1145-1154
Tremendous knowledge has been gained in the understanding of various modifications of IgG antibodies, driven mainly by the fact that antibodies are one of the most important groups of therapeutic molecules and because of the development of advanced analytical techniques. Recombinant monoclonal antibody (mAb) therapeutics expressed in mammalian cell lines and endogenous IgG molecules secreted by B cells in the human body share some modifications, but each have some unique modifications. Modifications that are common to recombinant mAb and endogenous IgG molecules are considered to pose a lower risk of immunogenicity. On the other hand, modifications that are unique to recombinant mAbs could potentially pose higher risk. The focus of this review is the comparison of frequently observed modifications of recombinant monoclonal antibodies to those of endogenous IgG molecules. 相似文献
15.
Patrick Mumm Dennis Imes Enrico Martinoia Khaled A.S. AI-Rasheid Dietmar Geiger Irene Marten Rainer Hedrich 《植物生理与分子生物学学报》2013,(5):1550-1563
Anion transporters in plants play a fundamental role in volume regulation and signaling. Currently, two plasma membrane-located anion channel familiesmSLAC/SLAH and ALMTmare known. Among the ALMT family, the root-expressed ALuminium-activated Malate Transporter 1 was identified by comparison of aluminum-tolerant and Al3+-sensitive wheat cultivars and was subsequently shown to mediate voltage-independent malate currents. In con- trast, ALMT12/QUAC1 (QUickly activating Anion Channel1) is expressed in guard cells transporting malate in an Al3+- insensitive and highly voltage-dependent manner. So far, no information is available about the structure and mechanism of voltage-dependent gating with the QUAC1 channel protein. Here, we analyzed gating of QUACl-type currents in the plasma membrane of guard cells and QUACl-expressing oocytes revealing similar voltage dependencies and activation- deactivation kinetics. In the heterologous expression system, QUAC1 was electrophysiologically characterized at increas- ing extra- and intracellular malate concentrations. Thereby, malate additively stimulated the voltage-dependent QUAC1 activity. In search of structural determinants of the gating process, we could not identify transmembrane domains com- mon for voltage-sensitive channels. However, site-directed mutations and deletions at the C-terminus of QUAC1 resulted in altered voltage-dependent channel activity. Interestingly, the replacement of a single glutamate residue, which is con- served in ALMT channels from different clades, by an alanine disrupted QUAC1 activity. Together with C- and N-terminal tagging, these results indicate that the cytosolic C-terminus is involved in the voltage-dependent gating mechanism of QUAC1. 相似文献
16.
Qurra-tul-Ann Afza Gardner Hooria Younas Muhammad Akhtar 《Biochimica et Biophysica Acta - Proteins and Proteomics》2013,1834(1):182-190
Human M-proinsulin was cleaved by trypsin at the R31R32–E33 and K64R65–G66 bonds (B/C and C/A junctions), showing the same cleavage specificity as exhibited by prohormone convertases 1 and 2 respectively. Buffalo/bovine M-proinsulin was also cleaved by trypsin at the K59R60–G61 bond but at the B/C junction cleavage occurred at the R31R32–E33 as well as the R31–R32E33 bond. Thus, the human isoform in the native state, with a 31 residue connecting C-peptide, seems to have a unique structure around the B/C and C/A junctions and cleavage at these sites is predominantly governed by the structure of the proinsulin itself. In the case of both the proinsulin species the cleavage at the B/C junction was preferred (65%) over that at the C/A junction (35%) supporting the earlier suggestion of the presence of some form of secondary structure at the C/A junction. Proinsulin and its derivatives, as natural substrates for trypsin, were used and mass spectrometric analysis showed that the kcat./Km values for the cleavage were most favourable for the scission of the bonds at the two junctions (1.02 ± 0.08 × 105 s− 1 M− 1) and the cleavage of the K29–T30 bond of M-insulin-RR (1.3 ± 0.07 × 105 s− 1 M− 1). However, the K29–T30 bond in M-insulin, insulin as well as M-proinsulin was shielded from attack by trypsin (kcat./Km values around 1000 s− 1 M− 1). Hence, as the biosynthetic path follows the sequence; proinsulin → insulin-RR → insulin, the K29–T30 bond becomes shielded, exposed then shielded again respectively. 相似文献
17.
Kenichi Harada Eiki Yamashita Atsushi Nakagawa Takamitsu Miyafusa Kouhei Tsumoto Takashi Ueno Yoshiharu Toyama Shigeki Takeda 《Biochimica et Biophysica Acta - Proteins and Proteomics》2013,1834(1):284-291
Bacteriophage Mu, which has a contractile tail, is one of the most famous genus of Myoviridae. It has a wide host range and is thought to contribute to horizontal gene transfer. The Myoviridae infection process is initiated by adhesion to the host surface. The phage then penetrates the host cell membrane using its tail to inject its genetic material into the host. In this penetration process, Myoviridae phages are proposed to puncture the membrane of the host cell using a central spike located beneath its baseplate. The central spike of the Mu phage is thought to be composed of gene 45 product (gp45), which has a significant sequence homology with the central spike of P2 phage (gpV). We determined the crystal structure of shortened Mu gp45Δ1-91 (Arg92–Gln197) at 1.5 Å resolution and showed that Mu gp45 is a needlelike structure that punctures the membrane. The apex of Mu gp45 and that of P2 gpV contained iron, chloride, and calcium ions. Although the C-terminal domain of Mu gp45 was sufficient for binding to the E. coli membrane, a mutant D188A, in which the Asp amino acid residue that coordinates the calcium ion was replaced by Ala, did not exhibit a propensity to bind to the membrane. Therefore, we concluded that calcium ion played an important role in interaction with the host cell membrane. 相似文献
18.
Carmen García-Ibarbia Jesús Delgado-Calle Iñigo Casafont Javier Velasco Jana Arozamena María I. Pérez-Núñez María A. Alonso María T. Berciano Fernando Ortiz José L. Pérez-Castrillón Agustín F. Fernández Mario F. Fraga María T. Zarrabeitia José A. Riancho 《Gene》2013
We reported previously that the expression of Wnt-related genes is lower in osteoporotic hip fractures than in osteoarthritis. We aimed to confirm those results by analyzing β-catenin levels and explored potential genetic and epigenetic mechanisms involved. 相似文献
19.
Escherichia coli topoisomerase I (EcTopoI) is a type IA bacterial topoisomerase which is receiving large attention due to its potential application as novel target for antibacterial therapeutics. Nevertheless, a detailed knowledge of its mechanism of action at molecular level is to some extent lacking. This is partly due to the requirement of several factors (metal ions, nucleic acid) to the proper progress of the enzyme catalytic cycle. Additionally, each of them can differently affect the protein structure. 相似文献
20.
Jovana Karoline Lima Neiva Leite Luciane Viater Turek Ricardo Lehtonen Rodrigues Souza Luciana da Silva Timossi Ana Claudia Vecchi Osiecki Raul Osiecki Lupe Furtado-Alle 《Gene》2013
Polymorphisms of butyrylcholinesterase (BChE) have been reported to be associated to weight, BMI variance and hypertriglyceridemia in adults and adolescents. The aim of the present study was to investigate the association of −116A (SNP: G/A; rs1126680) and 1914G (SNP: A/G; rs3495) variants of BCHE gene with anthropometric and biochemical variables associated with obesity in population sample of 115 individuals, from Southern Brazil. Participants were grouped in two categories: obese (BMI ≥ 30) and non-obese (BMI < 30). The 1914G allele showed significantly higher frequency in the obese group, and carriers of 1914G allele showed lower mean BChE activity when compared to 1914A carriers (p = 0.006). Higher means of BMI (p = 0.02) and triglyceride (TG; p = 0.01) were found in 1914G carriers (BMI = 27.57kg/m2; TG = 150.8 mg/dL) when compared to 1914A homozygotes (BMI = 25.55 kg/m2; TG = 107.9 mg/dL). Carriers of the −116A allele showed lower mean BChE activity than usual homozygotes, and the −116A variant was found in cis with 1914G (p < 0.0001; D′ = 1). The region of BCHE gene that contains the 1914G mutation site is target of microRNAs (miRs) and the response of BChE to glucocorticoids is especially influenced by these miRs. Therefore, it is possible that the 1914G allele can be interfering in gluconeogenesis, hyperglycemia, lipolysis and body fat distribution. This lower activity may cause an imbalance in lipid metabolism, which may lead to an increased predisposition to obesity and to a lower ability to maintain metabolic homeostasis. 相似文献