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141.
Binding sites in proteins can be either specifically functional binding sites (active sites) that bind specific substrates with high affinity or regulatory binding sites (allosteric sites), that modulate the activity of functional binding sites through effector molecules. Owing to their significance in determining protein function, the identification of protein functional and regulatory binding sites is widely acknowledged as an important biological problem. In this work, we present a novel binding site prediction method, Active and Regulatory site Prediction (AR-Pred), which supplements protein geometry, evolutionary, and physicochemical features with information about protein dynamics to predict putative active and allosteric site residues. As the intrinsic dynamics of globular proteins plays an essential role in controlling binding events, we find it to be an important feature for the identification of protein binding sites. We train and validate our predictive models on multiple balanced training and validation sets with random forest machine learning and obtain an ensemble of discrete models for each prediction type. Our models for active site prediction yield a median area under the curve (AUC) of 91% and Matthews correlation coefficient (MCC) of 0.68, whereas the less well-defined allosteric sites are predicted at a lower level with a median AUC of 80% and MCC of 0.48. When tested on an independent set of proteins, our models for active site prediction show comparable performance to two existing methods and gains compared to two others, while the allosteric site models show gains when tested against three existing prediction methods. AR-Pred is available as a free downloadable package at https://github.com/sambitmishra0628/AR-PRED_source . 相似文献
142.
Delphine Durette‐Morin Kimberley T. A. Davies Hansen D. Johnson Moira W. Brown Hilary Moors‐Murphy Bruce Martin Christopher T. Taggart 《Marine Mammal Science》2019,35(4):1280-1303
North Atlantic right whale monitoring in Roseway Basin, Canada, is primarily based on short‐term (<14 d) visual surveys conducted during August–September. Variability in survey effort has been the biggest limiting factor to studying changes in the population's occurrence and habitat use. Such efforts could be enhanced considerably using passive acoustic monitoring (PAM). We sought to determine if variation in whale presence, relative abundance, demography, and/or behavior (estimated through visual surveys) could be explained by variation in three right whale call types in this habitat. A generalized linear model was fit to 23 d of concurrent PAM and visual monitoring during four summers within the Roseway Basin Right Whale Critical Habitat boundaries. The model revealed significant positive relationships between relative abundance, call counts and presence of surface‐active group behavior. PAM can refine daily right whale presence estimates. While visual observations (n = 23 d) implied a 40% decline in right whale presence during 2014–2015 relative to 2004–2005, PAM data (n = 211 d) showed right whales were present between 71%–85% of survey days throughout all years analyzed. We demonstrate that PAM is a useful tool to extend periods of right whale monitoring, especially in areas where visual monitoring efforts may be limited. 相似文献
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144.
采用HPLC测定不同品种淫羊藿黄酮类即淫羊藿苷、朝藿定A、朝藿定B、朝藿定C4种有效成分含量,结合主成分分析对不同品种淫羊藿进行质量分析与评价,并考察淫羊藿对大鼠肾阳虚保护作用.将实验动物随机分为阳虚模型对照组(模型组)、金匮肾气丸干预组(阳性组)、淫羊藿低(125 mg/kg)、中(250 mg/kg)、高(500 ... 相似文献
145.
The mechanism of aconitase: 1.8 A resolution crystal structure of the S642a:citrate complex 下载免费PDF全文
Lloyd SJ Lauble H Prasad GS Stout CD 《Protein science : a publication of the Protein Society》1999,8(12):2655-2662
The crystal structure of the S642A mutant of mitochondrial aconitase (mAc) with citrate bound has been determined at 1.8 A resolution and 100 K to capture this binding mode of substrates to the native enzyme. The 2.0 A resolution, 100 K crystal structure of the S642A mutant with isocitrate binding provides a control, showing that the Ser --> Ala replacement does not alter the binding of substrates in the active site. The aconitase mechanism requires that the intermediate product, cis-aconitate, flip over by 180 degrees about the C alpha-C beta double bond. Only one of these two alternative modes of binding, that of the isocitrate mode, has been previously visualized. Now, however, the structure revealing the citrate mode of binding provides direct support for the proposed enzyme mechanism. 相似文献
146.
Rachel Kreisberg-Zakarin Ilya Borovok Michaela Yanko Yair Aharonowitz Gerald Cohen 《Antonie van Leeuwenhoek》1999,75(1-2):33-39
Isopenicillin N synthase is a key enzyme in the biosynthesis of penicillin and cephalosporin antibiotics, catalyzing the oxidative ring closure of -(L--aminoadipoyl)-L-cysteinyl-D-valine to form isopenicillin N. Recent advances in our understanding of the unique chemistry of this enzyme have come through the combined application of spectroscopic, molecular genetic and crystallographic approaches and led to important new insights into the structure and function of this enzyme. Here we review new information on the nature of the endogenous ligands that constitute the ferrous iron active site, sequence evidence for a novel structural motif involved in iron binding in this and related non-heme iron dependent dioxygenases, crystal structure studies on the enzyme and its substrate complex and the impact of these and site-directed mutagenesis studies for unraveling the mechanism of the isopenicillin N synthase reaction. 相似文献
147.
Structure of Pyridoxal Kinase from Sheep Brain and Role of the Tryptophanyl Residues 总被引:3,自引:0,他引:3
Bruno Maras Sofia Valiante Stefania Orru Maurizio Simmaco Donatella Barra Jorge E. Churchich 《Journal of Protein Chemistry》1999,18(3):259-268
The primary structure of sheep brain pyridoxal kinase has been determined by direct chemical and physical methods. The enzyme contains 312 amino acid residues with an acetylated methionine at the N-terminus, yielding a molecular mass of 34,861 Da. The functional role played by the two tryptophanyl residues in positions 52 and 244 of the polypeptide chain has been investigated by fluorescence spectroscopy. The tryptophanyl residues are not completely exposed to the rapidly relaxing solvent and they are poorly accessible to collisional quenchers. Chemical modification with NBS abolishes the catalytic activity of the kinase. The amino acid sequence of the sheep brain enzyme shows high similarity (86.2% identity) with the human pyridoxal kinase recently reported [Hanna, Turner, and Kirkness, (1997), J. Biol. Chem.
272, 10756–10760]. Comparison of the mammalian proteins with bacterial and yeast putative pyridoxal kinases retrieved from the Swiss-Prot data bank shows a low degree of overall similarity. In particular, the putative ATP-binding domain is conserved, whereas the region that appears to be crucial in the binding of the pyridoxal substrate is not. Thus, the assignment of the bacterial and yeast cDNA-deduced proteins as pyridoxal kinases should be taken with caution. 相似文献
148.
Prasad NS Raghavendra R Lokesh BR Naidu KA 《Prostaglandins, leukotrienes, and essential fatty acids》2004,70(6):521-528
A wide variety of phenolic compounds and flavonoids present in spices possess potent antioxidant, antimutagenic and anticarcinogenic activities. We examined whether 5-lipoxygenase (5-LO), the key enzyme involved in biosynthesis of leukotrienes is a possible target for the spices. Effect of aqueous extracts of turmeric, cloves, pepper, chili, cinnamon, onion and also their respective active principles viz., curcumin, eugenol, piperine, capsaicin, cinnamaldehyde, quercetin, and allyl sulfide were tested on human PMNL 5-LO activity by spectrophotomeric and HPLC methods. The formation of 5-LO product 5-HETE was significantly inhibited in a concentration-dependent manner with IC(50) values of 0.122-1.44 mg for aqueous extracts of spices and 25-83 microM for active principles, respectively. The order of inhibitory activity was of quercetin>eugenol>curcumin>cinnamaldehyde>piperine>capsaicin>allyl sulfide. Quercetin, eugenol and curcumin with one or more phenolic ring and methoxy groups in their structure showed high inhibitory effect, while the non-phenolic spice principle allyl sulfide showed least inhibitory effect on 5-LO. The inhibitory effect of quercetin, curcumin and eugenol was similar to that of synthetic 5-LO inhibitors-phenidone and NDGA. Moreover, the inhibitory potency of aqueous extracts of spice correlated with the active principles of their respective spices. The synergistic or antagonistic effect of mixtures of spice active principles and spice extracts were investigated and all the combinations of spice active principles/extracts exerted synergistic effect in inhibiting 5-LO activity. These findings clearly suggest that phenolic compounds present in spices might have physiological role in modulating 5-LO pathway. 相似文献
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150.
3alpha,17beta-Dihydroxy-3beta-methyl-5alpha-androstan-6-one (1) and 3beta,17beta-dihydroxy-3alpha-methyl-5alpha-androstan-6-one (13) were prepared by the reaction of methylmagnesium bromide with the 3-ketosteroids. Structures and configurations in position 3 were determined by NMR spectra. Substitution in the position 6 influences the ratio of the products. 相似文献