全文获取类型
收费全文 | 1551篇 |
免费 | 124篇 |
国内免费 | 1篇 |
专业分类
1676篇 |
出版年
2023年 | 6篇 |
2022年 | 12篇 |
2021年 | 29篇 |
2020年 | 17篇 |
2019年 | 19篇 |
2018年 | 18篇 |
2017年 | 25篇 |
2016年 | 36篇 |
2015年 | 66篇 |
2014年 | 93篇 |
2013年 | 81篇 |
2012年 | 124篇 |
2011年 | 119篇 |
2010年 | 89篇 |
2009年 | 73篇 |
2008年 | 117篇 |
2007年 | 102篇 |
2006年 | 105篇 |
2005年 | 80篇 |
2004年 | 86篇 |
2003年 | 82篇 |
2002年 | 76篇 |
2001年 | 21篇 |
2000年 | 13篇 |
1999年 | 17篇 |
1998年 | 21篇 |
1997年 | 21篇 |
1996年 | 15篇 |
1995年 | 15篇 |
1994年 | 10篇 |
1993年 | 11篇 |
1992年 | 8篇 |
1991年 | 9篇 |
1990年 | 12篇 |
1989年 | 7篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 6篇 |
1984年 | 5篇 |
1981年 | 3篇 |
1978年 | 2篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1964年 | 2篇 |
1959年 | 1篇 |
1955年 | 1篇 |
1954年 | 1篇 |
1925年 | 1篇 |
1919年 | 1篇 |
排序方式: 共有1676条查询结果,搜索用时 0 毫秒
91.
Gerda Oswald Ingo Rombeck B. Song H. Sigel B. Lippert 《Journal of biological inorganic chemistry》1998,3(3):236-245
The synthesis of cis-Pt(NH3)2(dCMP) is reported and by various physico-chemical methods it is demonstrated that it is a macrochelate in which Pt(II) is
bound simultaneously to the N3 site of cytosine in dCMP2– and to a phosphate-oxygen atom. According to the NOESY spectra (cross-peaks between cytosine H6 and H2′ and H3′) the cytosine
ring adopts an anti orientation. Highly unusual is the significant (1 ppm) downfield shift of the sugar proton H5″ in the 1H-NMR spectrum and the sensitivity of the cytosine H6 resonance on the protonation state of the phosphate group. Based on
these three features a geometry for the macrochelate is proposed. The compound is a major product of the reaction of cis-[Pt(NH3)2(H2O)2]2+ with dCMP2– at neutral pH, but it even forms at pH 5. By applying pD-dependent NMR spectroscopy (1H, 31P) and potentiometric pH titration, it is demonstrated that the Pt-coordinated phosphate group can be protonated (pK
a/1=3.21±0.10 and 3.31±0.05, respectively), and 1H- and 31P-NMR spectra also indicate deprotonation (pK
a/2=13.35±0.25) of the exocyclic amino group of the cytosine moiety. The metal ion binding affinity of cis-Pt(NH3)2(dCMP) is very small, as shown for Cu2+ (log K<0.6). The cis-Pt(NH3)2(dCMP) complex reacts with nucleosides and nucleotides (L′) by losing its chelate structure and forming mixed ligand complexes,
cis-Pt(NH3)2(dCMP)(L′); this means that the phosphate group is released from the coordination sphere of Pt(II), indicating that the Pt(II)-O(phosphate)
bond is not very strong.
Received: 23 October 1997 / Accepted: 17 February 1998 相似文献
92.
93.
94.
Ingo Rekittke Elena Olkhova Jochen Wiesner Ulrike Demmer Eberhard Warkentin Hassan Jomaa Ulrich Ermler 《FEBS letters》2013
Terpenoid precursor biosynthesis occurs in human and many pathogenic organisms via the mevalonate and 2-C-methyl-d-erythritol-4-phosphate (MEP) pathways, respectively. We determined the X-ray structure of the Fe/S containing (E)-4-hydroxy-3-methyl-but-2-enyl-diphosphate reductase (LytB) of the pathogenic protozoa Plasmodium falciparum which catalyzes the terminal step of the MEP pathway. The cloverleaf fold and the active site of P. falciparum LytB corresponds to those of the Aquifex aeolicus and Escherichia coli enzymes. Its distinct electron donor [2Fe–2S] ferredoxin was modeled to its binding site by docking calculations. The presented structural data provide a platform for a rational search of anti-malarian drugs. 相似文献
95.
96.
Anaerobic Ammonia Oxidation in the Presence of Nitrogen Oxides (NOx) by Two Different Lithotrophs 总被引:10,自引:0,他引:10 下载免费PDF全文
Ingo Schmidt Cristian Hermelink Katinka van de Pas-Schoonen Marc Strous Huub J. op den Camp J. Gijs Kuenen Mike S. M. Jetten 《Applied microbiology》2002,68(11):5351-5357
The anaerobic ammonia-oxidizing activity of the planctomycete Candidatus “Brocadia anammoxidans” was not inhibited by NO concentrations up to 600 ppm and NO2 concentrations up to 100 ppm. B. anammoxidans was able to convert (detoxify) NO, which might explain the high NO tolerance of this organism. In the presence of NO2, the specific ammonia oxidation activity of B. anammoxidans increased, and Nitrosomonas-like microorganisms recovered an NO2-dependent anaerobic ammonia oxidation activity. Addition of NO2 to a mixed population of B. anammoxidans and Nitrosomonas induced simultaneous specific anaerobic ammonia oxidation activities of up to 5.5 mmol of NH4+ g of protein−1 h−1 by B. anammoxidans and up to 1.5 mmol of NH4+ g of protein−1 h−1 by Nitrosomonas. The stoichiometry of the converted N compounds (NO2−/NH3 ratio) and the microbial community structure were strongly influenced by NO2. The combined activity of B. anammoxidans and Nitrosomonas-like ammonia oxidizers might be of relevance in natural environments and for technical applications. 相似文献
97.
We have dissected the molecular determinants involved in targeting the protein serine kinase PSKH1 to the endoplasmic reticulum (ER), the Golgi apparatus, and the plasma membrane (PM). Given this intracellular localization pattern, a potential role of PSKH1 in the secretory pathway was explored. The amino-terminal of PSKH1 revealed a striking similarity to the often acylated Src homology domain 4 (SH4)-harboring nonreceptor tyrosine kinases. Biochemical studies demonstrated that PSKH1 is myristoylated on glycine 2 and palmitoylated on cysteine 3. Dual amino-terminal acylation targets PSKH1 to Golgi as shown by colocalization with beta-COP and GM130, while nonpalmitoylated (myristoylated only) PSKH1 targets intracellular membranes colocalizing with protein disulphide isomerase (PDI, a marker for ER). Immunoelectron microscopy revealed that the dually acylated amino-terminal domain (in fusion with EGFP) was targeted to Golgi membranes as well as to the plasma membrane (PM), suggesting that the amino-terminal domain provides PSKH1 with membrane specificity dependent on its fatty acylation status. Subcellular fractionation by sucrose gradient analysis confirmed the impact of dual fatty acylation on endomembrane targeting, while cytosol and membrane fractioning revealed that myristoylation but not palmitoylation was required for general membrane association. A minimal region required for proper Golgi targeting of PSKH1 was identified within the first 29 amino acids. Expression of a PSKH1 mutant where the COOH-terminal kinase domain was swapped with green fluorescent protein and cysteine 3 was exchanged with serine resulted in disassembly of the Golgi apparatus as visualized by redistribution of beta-COP and GM130 to a diffuse cytoplasmic pattern, while leaving the tubulin skeleton intact. Our results suggest a structural and regulatory role of PSKH1 in maintenance of the Golgi apparatus, a key organelle within the secretory pathway. 相似文献
98.
Nitrosomonas eutropha, an obligately lithoautotrophic bacterium, was able to nitrify and denitrify simultaneously under anoxic conditions when
gaseous nitrogen dioxide (NO2) was supplemented to the atmosphere. In the presence of gaseous NO2, ammonia was oxidized, nitrite and nitric oxide (NO) were formed, and hydroxylamine occurred as an intermediate. Between
40 and 60% of the produced nitrite was denitrified to dinitrogen (N2). Nitrous oxide (N2O) was shown to be an intermediate of denitrification. Under an N2 atmosphere supplemented with 25 ppm NO2 and 300 ppm CO2, the amount of cell protein increased by 0.87 mg protein per mmol ammonia oxidized, and the cell number of N. eutropha increased by 5.8 × 109 cells per mmol ammonia oxidized. In addition, the ATP and NADH content increased by 4.3 μmol ATP (g protein)–1 and 6.3 μmol NADH (g protein)–1 and was about the same in both anaerobically and aerobically grown cells. Without NO2, the ATP content decreased by 0.7 μmol (g protein)–1, and the NADH content decreased by 1.2 μmol (g protein)–1. NO was shown to inhibit anaerobic ammonia oxidation.
Received: 9 October 1996 / Accepted: 5 December 1996 相似文献
99.
Kekenes-Huskey PM Muegge I von Rauch M Gust R Knapp EW 《Bioorganic & medicinal chemistry》2004,12(24):794-6537
Numerous selective estrogen receptor modulators (SERMs) have been synthesized and assayed in recent years. The focus of this study is to apply coarse-grain molecular docking procedures coupled with fine-grain all-atom force field optimization strategies to shed light on the binding mechanisms of currently available estrogen receptor-active compounds. Although the mechanics of ligand binding in estrogen receptors is generally well understood, there is room for surprises. In this paper computational evidence corroborating the experimentally observed type I agonistic binding mode for estradiol (E2) and diethylstilbesterol (DES) and the type II antagonistic binding mode for 4-hydroxytamoxifen and raloxifen is presented. Included in this type I agonistic mode are the DES derivatives, transstilbene and 1,2-diaryldiaminoethane. In addition, a novel ‘type II agonistic’ binding mode for 2,3-diarylimidazolines, 4,5-diarylimidazoles, 2,3-diarylpiperazines is introduced. This mode is stabilized by suggesting alternative hydrogen bond anchor points in the ligand binding domain as potential leads for future drug design. 相似文献
100.
Michael Motz Ingo Kober Charles Girardot Eva Loeser Ulrike Bauer Michael Albers Gerd Moeckel Eric Minch Hartmut Voss Christian Kilger Manfred Koegl 《The Journal of biological chemistry》2002,277(18):16179-16188
Thermostable DNA polymerases are an important tool in molecular biology. To exploit the archaeal repertoire of proteins involved in DNA replication for use in PCR, we elucidated the network of proteins implicated in this process in Archaeoglobus fulgidus. To this end, we performed extensive yeast two-hybrid screens using putative archaeal replication factors as starting points. This approach yielded a protein network involving 30 proteins potentially implicated in archaeal DNA replication including several novel factors. Based on these results, we were able to improve PCR reactions catalyzed by archaeal DNA polymerases by supplementing the reaction with predicted polymerase co-factors. In this approach we concentrated on the archaeal proliferating cell nuclear antigen (PCNA) homologue. This protein is known to encircle DNA as a ring in eukaryotes, tethering other proteins to DNA. Indeed, addition of A. fulgidus PCNA resulted in marked stimulation of PCR product generation. The PCNA-binding domain was determined, and a hybrid DNA polymerase was constructed by grafting this domain onto the classical PCR enzyme from Thermus aquaticus, Taq DNA polymerase. Addition of PCNA to PCR reactions catalyzed by the fusion protein greatly stimulated product generation, most likely by tethering the enzyme to DNA. This sliding clamp-induced increase of PCR performance implies a promising novel micromechanical principle for the development of PCR enzymes with enhanced processivity. 相似文献