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991.
Parthasarathy Sampathkumar Frances Lu Xun Zhao Zhenzhen Li Jeremiah Gilmore Kevin Bain Marc E. Rutter Tarun Gheyi Kenneth D. Schwinn Jeffrey B. Bonanno Ursula Pieper J. Eduardo Fajardo Andras Fiser Steven C. Almo Subramanyam Swaminathan Mark R. Chance David Baker Shane Atwell Devon A. Thompson J. Spencer Emtage Stephen R. Wasserman Andrej Sali J. Michael Sauder Stephen K. Burley 《Proteins》2010,78(14):3056-3062
992.
993.
Group II chaperonins, found in eukaryotic and archaeal organisms, recognize substrate proteins through diverse mechanisms that involve either hydrophobic‐ or electrostatic‐dominated interactions. This action is distinct from the universal substrate recognition mechanism of group I chaperonins, which bind a wide spectrum of non‐native proteins primarily through hydrophobic interactions. We use computational approaches to pinpoint the substrate protein binding sites of the γ‐subunit of the eukaryotic chaperonin CCT and to identify its interactions with the stringent substrate β‐tubulin. Protein–protein docking methods reveal intrinsic binding sites of CCT comprising a helical (HL) region, homologous to the GroEL‐binding site, and the helical protrusion (HP) region. We performed molecular dynamics simulations of the solvated CCTγ apical domain, β‐tubulin peptide‐CCTγ complexes, and isolated β‐tubulin peptides. We find that tubulin binds to CCTγ through an extensive interface that spans both the HL region and the HP region. HL interactions involve both hydrophobic and electrostatic contacts, while binding to the HP region is stabilized almost exclusively by a salt bridge network. On the basis of additional simulations of a β‐tubulin‐CCTγ complex that involves a reduced interface, centered onto the HP region, we conclude that this salt bridge network is the minimal stabilizing interaction required. Strong conservation of the charged amino acids that participate in the salt bridge network, Arg306 and Glu271, indicates a general mechanism across the nonidentical CCT subunits and group II chaperonins. Proteins 2010. © 2009 Wiley‐Liss, Inc. 相似文献
994.
Horseradish peroxidase was verified to catalyze, without any phenol, the hydrogen peroxide oxidation of chlorophyll a (Chl a), solubilized with Triton X-100. The 132(S) and 132(R) diastereomers of 132-hydroxyChl a were characterized as major oxidation products (ca. 60%) by TLC on sucrose, UV-vis, 1H, and 13C NMR spectra, as well as fast-atom bombardment MS. A minor amount of the 152-methyl, 173-phytyl ester of Mg-unstable chlorin was identified on the basis of its UV-vis spectrum and reactivity with diazomethane, which converted it to the 131,152-dimethyl, 173-phytyl ester of Mg-purpurin 7. The side products (ca. 10%) were suggested to include the 173-phytyl ester of Mg-purpurin 18, which is known to form easily from the Mg-unstable chlorin. The side products also included two red components with UV-vis spectral features resembling those of pure Chl a enolate anion. Hence, the two red components were assigned to the enolate anions of Chl a and pheophytin a or, alternatively, two different complexes of the Chl a enolate ion with Triton X-100. All the above products characterized by us are included in our published free-radical allomerization mechanism of Chl a, i.e. oxidation by ground-state dioxygen. The HRP clearly accelerated the allomerization process, but it did not produce bilins, that is, open-chain tetrapyrroles, the formation of which would require oxygenolysis of the chlorin macrocycle. In this regard, our results are in discrepancy with the claim by several researchers that ‘bilirubin-like compounds’ are formed in the HRP-catalyzed oxidation of Chl a. Inspection of the likely reactions that occurred on the distal side of the heme in the active centre of HRP provided a reasonable explanation for the observed catalytic effect of the HRP on the allomerization of Chl. In the active centre of HRP, the imidazole nitrogen of His-42 was considered to play a crucial role in the C-132 deprotonation of Chl a, which resulted in the Chl a enolate ion resonance hybrid. The Chl enolate was then oxidized to the Chl 132-radical while the HRP Compound I was reduced to Compound II. The same reactive Chl derivatives, i.e. the Chl enolate anion and the Chl 132-radical, which are produced twice in the HRP reaction cycle, happen to be the crucial intermediates in the initial stages of the Chl allomerization mechanism. 相似文献
995.
Emma A. Higgins Doreen S. Boyd Tom W. Brown Sarah C. Owen Adam C. Algar 《Ecology and evolution》2021,11(16):11414
The question of what controls animal abundance has always been fundamental to ecology, but given rapid environmental change, understanding the drivers and mechanisms governing abundance is more important than ever. Here, we determine how multidimensional environments and niches interact to determine population abundance along a tropical habitat gradient. Focusing on the endemic lizard Anolis bicaorum on the island of Utila (Honduras), we evaluate direct and indirect effects of three interacting niche axes on abundance: thermal habitat quality, structural habitat quality, and prey availability. We measured A. bicaorum abundance across a series of thirteen plots and used N‐mixture models and path analysis to disentangle direct and indirect effects of these factors. Results showed that thermal habitat quality and prey biomass both had positive direct effects on anole abundance. However, thermal habitat quality also influenced prey biomass, leading to a strong indirect effect on abundance. Thermal habitat quality was primarily a function of canopy density, measured as leaf area index (LAI). Despite having little direct effect on abundance, LAI had a strong overall effect mediated by thermal quality and prey biomass. Our results demonstrate the role of multidimensional environments and niche interactions in determining animal abundance and highlight the need to consider interactions between thermal niches and trophic interactions to understand variation in abundance, rather than focusing solely on changes in the physical environment. 相似文献
996.
Robin E. Duncan Yuhui Wang Maryam Ahmadian Jennifer Lu Eszter Sarkadi-Nagy Hei Sook Sul 《Journal of lipid research》2010,51(2):309-317
Murine desnutrin/human ATGL is a triacylglycerol (TAG) hydrolase with a predicted catalytic dyad within an α-β hydrolase fold in the N-terminal region. In humans, mutations resulting in C-terminal truncation cause neutral lipid storage disease with myopathy. To identify critical functional domains, we measured TAG breakdown in cultured cells by mutated or truncated desnutrin. In vitro, C-terminally truncated desnutrin displayed an even higher apparent Vmax than the full-length form without changes in Km, which may be explained by our finding of an interaction between the C- and N-terminal domains. In live cells, however, C-terminally truncated adenoviral desnutrin had lower TAG hydrolase activity. We investigated a role for the phosphorylation of C-terminal S406 and S430 residues but found that these were not necessary for TAG breakdown or lipid droplet localization in cells. The predicted N-terminal active sites, S47 and D166, were both critical for TAG hydrolysis in live cells and in vitro. We also identified two overlapping N-terminal motifs that predict lipid substrate binding domains, a glycine-rich motif (underlined) and an amphipathic α-helix (bold) within amino acid residues 10–24 (ISFAGCGFLGVYHIG). G14, F17, L18, and V20, but not G16 and G19, were important for TAG hydrolysis, suggesting a potential role for the amphipathic α-helix in TAG binding. This study identifies for the first time critical sites in the N-terminal region of desnutrin and reveals the requirement of the C-terminal region for TAG hydrolysis in cultured cells. 相似文献
997.
Proteolysis is important for protein quality control and for the proper regulation of many intracellular processes in prokaryotes and eukaryotes. Discerning substrates from other cellular proteins is a key aspect of proteolytic function. The Escherichia coli HslUV protease is a member of a major family of ATP-dependent AAA+ degradation machines. HslU hexamers recognize and unfold native protein substrates and then translocate the polypeptide into the degradation chamber of the HslV peptidase. Although a wealth of structural information is available for this system, relatively little is known about mechanisms of substrate recognition. Here, we demonstrate that mutations in the unstructured N-terminal and C-terminal sequences of two model substrates alter HslUV recognition and degradation kinetics, including changes in Vmax. By introducing N- or C-terminal sequences that serve as recognition sites for specific peptide-binding proteins, we show that blocking either terminus of the substrate interferes with HslUV degradation, with synergistic effects when both termini are obstructed. These results support a model in which one terminus of the substrate is tethered to the protease and the other terminus is engaged by the translocation/unfolding machinery in the HslU pore. Thus, degradation appears to consist of discrete steps, which involve the interaction of different terminal sequence signals in the substrate with different receptor sites in the HslUV protease. 相似文献
998.
Vinothkumar KR Strisovsky K Andreeva A Christova Y Verhelst S Freeman M 《The EMBO journal》2010,29(22):3797-3809
Rhomboids are intramembrane proteases that use a catalytic dyad of serine and histidine for proteolysis. They are conserved in both prokaryotes and eukaryotes and regulate cellular processes as diverse as intercellular signalling, parasitic invasion of host cells, and mitochondrial morphology. Their widespread biological significance and consequent medical potential provides a strong incentive to understand the mechanism of these unusual enzymes for identification of specific inhibitors. In this study, we describe the structure of Escherichia coli rhomboid GlpG covalently bound to a mechanism‐based isocoumarin inhibitor. We identify the position of the oxyanion hole, and the S1‐ and S2′‐binding subsites of GlpG, which are the key determinants of substrate specificity. The inhibitor‐bound structure suggests that subtle structural change is sufficient for catalysis, as opposed to large changes proposed from previous structures of unliganded GlpG. Using bound inhibitor as a template, we present a model for substrate binding at the active site and biochemically test its validity. This study provides a foundation for a structural explanation of rhomboid specificity and mechanism, and for inhibitor design. 相似文献
999.
Sai Chetan K Sukuru Florian Nigsch Jean Quancard Martin Renatus Rajiv Chopra Natasja Brooijmans Dmitri Mikhailov Zhan Deng Allen Cornett Jeremy L Jenkins Ulrich Hommel John W Davies Meir Glick 《Protein science : a publication of the Protein Society》2010,19(11):2096-2109
We present here a comprehensive analysis of proteases in the peptide substrate space and demonstrate its applicability for lead discovery. Aligned octapeptide substrates of 498 proteases taken from the MEROPS peptidase database were used for the in silico analysis. A multiple‐category naïve Bayes model, trained on the two‐dimensional chemical features of the substrates, was able to classify the substrates of 365 (73%) proteases and elucidate statistically significant chemical features for each of their specific substrate positions. The positional awareness of the method allows us to identify the most similar substrate positions between proteases. Our analysis reveals that proteases from different families, based on the traditional classification (aspartic, cysteine, serine, and metallo), could have substrates that differ at the cleavage site (P1–P1′) but are similar away from it. Caspase‐3 (cysteine protease) and granzyme B (serine protease) are previously known examples of cross‐family neighbors identified by this method. To assess whether peptide substrate similarity between unrelated proteases could reliably translate into the discovery of low molecular weight synthetic inhibitors, a lead discovery strategy was tested on two other cross‐family neighbors—namely cathepsin L2 and matrix metallo proteinase 9, and calpain 1 and pepsin A. For both these pairs, a naïve Bayes classifier model trained on inhibitors of one protease could successfully enrich those of its neighbor from a different family and vice versa, indicating that this approach could be prospectively applied to lead discovery for a novel protease target with no known synthetic inhibitors. 相似文献
1000.
番茄基质通气栽培模式的效果 总被引:14,自引:0,他引:14
针对雾培模式在提高作物产量同时增加无土栽培成本的问题,研制了一种新型的珍珠岩通气栽培模式,探讨了其对番茄的栽培效果.试验设计3种栽培方式:全珍珠岩栽培(CK),珍珠岩通气栽培(T1)和气雾培(T2).结果表明:T1可显著改善番茄根际通气环境,其中根际CO2浓度仅为CK的1/5,O2浓度则为CK的1.17倍;显著增加了番茄的株高和茎粗,在定植后60d时,株高和茎粗分别比CK增加了5.1%和8.4%;植株净光合速率显著高于CK,在净光合速率达到最大值(定植后45d)时,比CK提高了13%;显著提高了植株根系活力和吸收能力,在定植后45d时,其根系活力为CK的1.23倍,在定植后60d时,根系钾、钙、镁含量分别比CK增加了31%、37%和27%,番茄产量为CK的1.16倍.且T1上述指标均与T2无显著差异;而CK、T1和T2在果实的可溶性糖、有机酸、糖酸比方面无显著差异.表明以珍珠岩为基质的通气栽培模式简便易行且可显著提高番茄产量. 相似文献