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81.
Saskia Vanderhaegen Marcus Fislage Katarzyna Domanska Wim Versées Els Pardon Vittorio Bellotti Jan Steyaert 《Protein science : a publication of the Protein Society》2013,22(10):1349-1357
To investigate early intermediates of β2‐microglobulin (β2m) amyloidogenesis, we solved the structure of β2m containing the amyloidogenic Pro32Gly mutation by X‐ray crystallography. One nanobody (Nb24) that efficiently blocks fibril elongation was used as a chaperone to co‐crystallize the Pro32Gly β2m monomer under physiological conditions. The complex of P32G β2m with Nb24 reveals a trans peptide bond at position 32 of this amyloidogenic variant, whereas Pro32 adopts the cis conformation in the wild‐type monomer, indicating that the cis to trans isomerization at Pro32 plays a critical role in the early onset of β2m amyloid formation. 相似文献
82.
Rémy Bertrand Teponno Azefack Léon Tapondjou Eliane Abou-Mansour H Stoeckli-Evans Pierre Tane Luciano Barboni 《Phytochemistry》2008,69(12):2374-2379
From the bulbils of Dioscorea bulbifera L. var sativa, two clerodane diterpenoids, Bafoudiosbulbins F (1) and G (2), together with five known compounds: Bafoudiosbulbins A-C, 3,5,4'-trihydroxy-3'-methoxybibenzyl, and kaempferol were isolated. Their structures were established by spectroscopic techniques, including (1)H, (13)C NMR, NOESY, ROESY, COSY, TOCSY, HSQC, and HMBC. The relative stereochemistry of compounds 1 and 2 was assigned on the basis of X-ray crystallographic diffraction analysis. Furthermore, the structure of Bafoudiosbulbin B was revised using extensive 2D NMR techniques as well as chemical transformation. 相似文献
83.
Zn对细胞保护作用机理的研究 总被引:16,自引:0,他引:16
应用扫描质子微探针和同步辐射x荧光分析技术测定了细胞中元素的分布和组成,为确定Zn是细胞结构成分提供了直接的实验依据.用上述核技术结合有关生化指标,分析测定了正常和损伤细胞(脂质过氧化损伤)中Fe,Zn和丙二醛、SH基含量变化的相互关系.实验结果表明,当细胞发生脂质过氧化损伤时,Fe含量和丙二醛含量同步增高,而Zn含量和SH基量则降低.给细胞补充Zn后,提高了细胞质膜中的Zn含量,SH基量也随之增加,同时丙二醛量降低.提示Zn保护细胞完整性的作用机理之一是控制脂质过氧化作用.Zn可保护膜蛋白的SH基,减少和阻止被Fe所催化的过氧化反应. 相似文献
84.
Crystal structures of thrombin complexed with two spin labels called para-V, 4-(2,2,5,5-tetramethyl-pyrrolidine-1-oxyl)-p-(fluorosulfonyl) benzamidine, and meta-V, 3-(2,2,5,5-tetramethyl-pyrrolidine-1-oxyl)-m-(fluorosulfonyl) benzamidine, have been completed at 2.0 and 3.0 Å resolution, respectively. Previous electron spin resonance studies with these labels gave rise to a low-resolution topography map of thrombin's extended active site. These labels monitor two distinct areas of the thrombin active site: (1) an apolar binding site which manifests itself in an biphasic activation/inhibition effect on thrombin activity and (2) a region sensitive to -thrombin autoproteolytic cleavage(s) to -thrombin (Arg75-Tyr76 and/or Arg77A-Asn78, and Lys149E-Gly150, chymotrypsin numbering). Para-V was found to bind along the substrate binding cleft, while meta-V was found to bind both at the substrate primary specificity pocket and at a site which interacts with the -cleavage loop. These studies reaffirm that accurate information may be gained from solution studies and indicates the complementarity of solid-state studies. 相似文献
85.
The 1:1 inclusion complex of β-cyclodextrin and p-aminobenzoic acid was prepared and characterized by TG-DTA. The crystal structure of the complex was solved directly from powder X-ray diffraction data using the direct space approach and refined using Rietveld refinement techniques. The complex crystallizes in monoclinic P21 space group, with unit cell parameters a = 20.7890 ?, b = 10.2084 ?, c = 15.1091 ?, β = 110.825°, V = 2997 ?3. The amino group is located at the wide side of the β-cyclodextrin cavity, forming hydrogen bonds with β-cyclodextrin, and the carboxyl group is located at the narrow side. The crystallographic data obtained from powder diffraction data were compared with the single crystallographic data, and the result shows that solving crystal structure of cyclodextrins inclusion complexes of such complexity is accessible to powder diffractionists to some extent. 相似文献
86.
Jang do S Lee HJ Lee B Hong BH Cha HJ Yoon J Lim K Yoon YJ Kim J Ree M Lee HC Choi KY 《FEBS letters》2006,580(17):4166-4171
Failure to detect the intermediate in spite of its existence often leads to the conclusion that two-state transition in the unfolding process of the protein can be justified. In contrast to the previous equilibrium unfolding experiment fitted to a two-state model by circular dichroism and fluorescence spectroscopies, an equilibrium unfolding intermediate of a dimeric ketosteroid isomerase (KSI) could be detected by small angle X-ray scattering (SAXS) and analytical ultracentrifugation. The sizes of KSI were determined to be 18.7A in 0M urea, 17.3A in 5.2M urea, and 25.1A in 7M urea by SAXS. The size of KSI in 5.2M urea was significantly decreased compared with those in 0M and 7M urea, suggesting the existence of a compact intermediate. Sedimentation velocity as obtained by ultracentrifugation confirmed that KSI in 5.2M urea is distinctly different from native and fully-unfolded forms. The sizes measured by pulse field gradient nuclear magnetic resonance (NMR) spectroscopy were consistent with those obtained by SAXS. Discrepancy of equilibrium unfolding studies between size measurement methods and optical spectroscopies might be due to the failure in detecting the intermediate by optical spectroscopic methods. Further characterization of the intermediate using (1)H NMR spectroscopy and Kratky plot supported the existence of a partially-folded form of KSI which is distinct from those of native and fully-unfolded KSIs. Taken together, our results suggest that the formation of a compact intermediate should precede the association of monomers prior to the dimerization process during the folding of KSI. 相似文献
87.
Crystals of ribosomal protein L6 from Bacillus stearothermophilus suitable for high resolution structural studies have been obtained. Crystals are hexagonal with space group P6122 (or the enantiomorph P6522) and cell dimensions a = b = 72.7 Å, c = 124.9 Å. A search for heavy atom derivatives is in progress. 相似文献
88.
The polymorphic phase behaviour of dilinoleoylphosphatidyethanolamine (DLPE) and 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) is investigated by freeze-fracture electron microscopy, X-ray diffraction and 31P-NMR. The structures at 5% or less POPC are predominantly inverted hexagonal (HII), whereas at 15% or more POPC, the structure is mostly bilayer (L), interrupted by defects (lipidic particles). A cubic phase structure is observed in the transition range between H and L phases; the cubic arrangement deteriorates at higher temperatures into an amorphous aggregate of spherical units. Both cubic and amorphous structures contribute to the isotropic 31P resonance, with no preference for PC or PE partitioning in the isotropic motion as observed by high resolution NMR. The existence of the cubic phase seems to depend critially on the homogeneity and the degree unsaturation of the phospholipids. 相似文献
89.
The P-loop-containing protein phos-phatases are important regulators in signal transduction. These enzymes have structural and functional similarity with a conserved sequence of Dx(25-41)HCxxGxxR(T/S) essential for catalysis. The singular protein tyrosine phosphatase (PTP) from archaeal Sulfolobus solfataricus is one of the smallest known PTPs with extreme thermostability. Here, we report the crystal structure of this phosphatase and its complexes with two tyrosyl phosphopeptides A-(p)Y-R and N-K-(p)Y-G-N. The structure suggests the minimal structural motif of the PTP family, having two variable sequences inserted between the beta2-beta3 and beta3-beta4 strands, respectively. The phosphate of both phosphopeptide substrates is bound to the P-loop through several hydrogen bonds. Comparison of several phosphatase-substrate complexes revealed that Gln135 on the Q-loop has different modes of recognition toward phosphopeptides. The substrate specificity of SsoPTP is primarily localized at the phosphotyrosine, suggesting that this phosphatase may be a prototypical PTP. 相似文献
90.
Shigella dysentriae and other Gram‐negative human pathogens are able to use iron from heme bound to hemoglobin for growing. We solved at 2.6 Å resolution the 3D structure of the TonB‐dependent heme/hemoglobin outer membrane receptor ShuA from S. dysenteriae. ShuA binds to hemoglobin and transports heme across the outer membrane. The structure consists of a C‐terminal domain that folds into a 22‐stranded transmembrane β‐barrel, which is filled by the N‐terminal plug domain. One distal histidine ligand of heme is located at the apex of the plug, exposed to the solvent. His86 is situated 9.86 Å apart from His420, the second histidine involved in the heme binding. His420 is in the extracellular loop L7. The heme coordination by His86 and His420 involves conformational changes. The comparisons with the hemophore receptor HasR of Serratia marcescens bound to HasA‐Heme suggest an extracellular induced fit mechanism for the heme binding. The loop L7 contains hydrophobic residues which could interact with the hydrophobic porphyring ring of heme. The energy required for the transport by ShuA is derived from the proton motive force after interactions between the periplasmic N‐terminal TonB‐box of ShuA and the inner membrane protein, TonB. In ShuA, the TonB‐box is buried and cannot interact with TonB. The structural comparisons with HasR suggest its conformational change upon the heme binding for interacting with TonB. The signaling of the heme binding could involve a hydrogen bond network going from His86 to the TonB‐box. Proteins 2010. © 2009 Wiley‐Liss, Inc. 相似文献