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121.
The conformations of four BK antagonists, [D-Arg 0, Hyp3, Thi5, D-Phe7, Acc8]BK (1), Aaa[D-Arg 0, Hyp3, Thi5, D-Phe7, Acc8]BK (2), [D-Arg 0, Hyp3, Thi5, 8, Apc7]BK (3), and Aaa[D-Arg(0), Hyp(3), Thi(5, 8), Apc7]BK (4) were studied by using 2D NMR spectroscopy and MD simulations with time-averaged (TAV) restraints. According to the results of the NMR measurements, the BK antagonists contain 7-30% of minor conformation resulting from cis/trans isomerization of the peptide bonds preceding either Pro or Hyp residues. The major conformation of each peptide possesses all peptide bonds in trans configuration. Peptides modified with the Apc residue at position 7 (peptides 3 and 4) possess a higher percentage of minor isomer.Peptide 1 exhibits the strongest vasodepressor potency among the analogs studied and as a single one forms the betaII-turn in the 2-5 fragment, which is believed to be crucial for antagonistic activity. This peptide is also the most compact. The radius of gyration (Rg) amounts to 6.9 A and is by ca 1.5 A lower than that of the remaining analogs. With peptide 4, the ST-turn of type I within the Ser6-Thi8 fragment was found. 相似文献
122.
JarosŁaw Ruczyński Brygida Lewandowska Piotr Mucha Piotr Rekowski 《Journal of peptide science》2008,14(3):335-341
The sequence-dependent, acid- or base-catalysed aspartimide formation is one of the most serious side reactions in solid-phase synthesis of peptides containing aspartic acid. In the present work, we investigated the susceptibility of 4-(N-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl]amino)benzyl (Dmab), an aspartic acid beta-carboxy side-chain protecting group, for aspartimide formation. As a model, 15-amino acid-residue galanin fragment analogue containing the Asp-Ala motif was used during Fmoc-based solid-phase synthesis. Our study showed a strong tendency of Dmab-protected peptide to form aspartimide with unusual high efficiency. Furthermore, to investigate the susceptibility of Asp-Ala motif for aspartimide formation during the synthesis using Asp(ODmab), a 5-amino acid-residue galanin fragment LGPDA, different types of resin linkers, variety of Fmoc-deprotection conditions and coupling methods were applied. 相似文献
123.
Prochorec-Sobieszek M Rymkiewicz G Makuch-Łasica H Majewski M Michalak K Rupiński R Warzocha K Maryniak R 《Arthritis research & therapy》2008,10(3):R55-12
Introduction
The purpose of this study was to analyze the data of patients with T-cell large granular lymphocyte (T-LGL) lymphocytosis associated with inflammatory arthropathy or with no arthritis symptoms.Methods
Clinical, serological as well as histopathological, immuhistochemical, and flow cytometric evaluations of blood/bone marrow of 21 patients with T-LGL lymphocytosis were performed. The bone marrow samples were also investigated for T-cell receptor (TCR) and immunoglobulin (IG) gene rearrangements by polymerase chain reaction with heteroduplex analysis.Results
Neutropenia was observed in 21 patients, splenomegaly in 10, autoimmune diseases such as rheumatoid arthritis (RA) in 9, unclassified arthritis resembling RA in 2, and autoimmune thyroiditis in 5 patients. T-LGL leukemia was recognized in 19 cases. Features of Felty syndrome were observed in all RA patients, representing a spectrum of T-LGL proliferations from reactive polyclonal through transitional between reactive and monoclonal to T-LGL leukemia. Bone marrow trephines from T-LGL leukemia patients showed interstitial clusters and intrasinusoidal linear infiltrations of CD3+/CD8+/CD57+/granzyme B+ lymphocytes, reactive lymphoid nodules, and decreased or normal granulocyte precursor count with left-shifted maturation. In three-color flow cytometry (FCM), T-LGL leukemia cells demonstrated CD2, CD3, and CD8 expression as well as a combination of CD16, CD56, or CD57. Abnormalities of other T-cell antigen expressions (especially CD5, CD7, and CD43) were also detected. In patients with polyclonal T-LGL lymphocytosis, T cells were dispersed in the bone marrow and the expression of pan-T-cell antigens in FCM was normal. Molecular studies revealed TCRB and TCRG gene rearrangements in 13 patients and TCRB, TCRG, and TCRD in 4 patients. The most frequently rearranged regions of variable genes were Vβ-Jβ1, Jβ2 and Vγ If Vγ10-Jγ. Moreover, in 4 patients, additional rearrangements of IG kappa and lambda variable genes of B cells were also observed.Conclusion
RA and neutropenia patients represented a continuous spectrum of T-LGL proliferations, although monoclonal expansions were most frequently observed. The histopathological pattern and immunophenotype of bone marrow infiltration as well as molecular characteristics were similar in T-LGL leukemia patients with and without arthritis. 相似文献124.
Łukasz Jaremko Mariusz Jaremko Paweł Pasikowski Marek Cebrat Piotr Stefanowicz Marek Lisowski Jolanta Artym Michał Zimecki Igor Zhukov Zbigniew Szewczuk 《Biopolymers》2009,91(6):423-431
Recently, ubiquitin was suggested as a promising anti‐inflammatory protein therapeutic. We found that a peptide fragment corresponding to the ubiquitin50–59 sequence (LEDGRTLSDY) possessed the immunosuppressive activity comparable with that of ubiquitin. CD and NMR spectroscopies were used to determine the conformational preferences of LEDGRTLSDY in solution. The peptide mixture, obtained by pepsin digestion of ubiquitin, was even more potent than the intact protein. Although the peptide exhibited a well‐defined conformation in methanol, its structure was distinct from the corresponding 50–59 fragment in the native ubiquitin molecule. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 423–431, 2009. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com 相似文献
125.
Biodegradation of diesel fuel by a microbial consortium in the presence of 1-alkoxymethyl-2-methyl-5-hydroxypyridinium chloride homologues 总被引:1,自引:0,他引:1
Łukasz Chrzanowski Monika Stasiewicz Mikołaj Owsianiak Alicja Szulc Agnieszka Piotrowska-Cyplik Agnieszka K. Olejnik-Schmidt Bogdan Wyrwas 《Biodegradation》2009,20(5):661-671
Fast development of ionic liquids as gaining more and more attention valuable chemicals will undoubtedly lead to environmental
pollution. New formulations and application of ionic liquids may result in contamination in the presence of hydrophobic compounds,
such as petroleum mixtures. We hypothesize that in the presence of diesel fuel low-water-soluble ionic liquids may become
more toxic to hydrocarbon-degrading microorganisms. In this study the influence of 1-alkoxymethyl-2-methyl-5-hydroxypyridinium
chloride homologues (side-chain length from C3 to C18) on biodegradation of diesel fuel by a bacterial consortium was investigated. Whereas test performed for the consortium cultivated
on disodium succinate showed that toxicity of the investigated ionic liquids decreased with increase in side-chain length,
only higher homologues (C8–C18) caused a decrease in diesel fuel biodegradation. As a result of exposure to toxic compounds also modification in cell surface
hydrophobicity was observed (MATH). Disulphine blue active substances method was employed to determine partitioning index
of ionic liquids between water and diesel fuel phase, which varied from 1.1 to 51% for C3 and C18 homologues, respectively. We conclude that in the presence of hydrocarbons acting as a solvent, the increased bioavailability
of hydrophobic homologues is responsible for the decrease in biodegradation efficiency of diesel fuel. 相似文献
126.
Dorota Łażewska Kamil Kuder Xavier Ligneau Jean-Claude Camelin Walter Schunack Holger Stark Katarzyna Kieć-Kononowicz 《Bioorganic & medicinal chemistry》2009,17(8):3037-3042
Synthesis and biological activities of a series of homo- or substituted piperidine unsymmetrical diethers are described. The novel compounds were evaluated for histamine H3 receptor binding affinities at recombinant human H3 receptor stably expressed in HEK-293 cells. All diethers showed in vitro affinities in nanomolar concentration range. The most potent compounds are 1-[3-(3-(4-chlorophenoxy)propoxy)propyl]-3-methylpiperidine 11 (Ki = 3.2 nM) and 1-[3-(3-(4-chlorophenoxy)propoxy)propyl]azepane 13 (Ki = 3.5 nM). 相似文献
127.
M. Parczewski M. Leszczyszyn-Pynka M. Kaczmarczyk G. Adler A. Bińczak-Kuleta B. Łoniewska A. Boroń-Kaczmarska A. Ciechanowicz 《Journal of applied genetics》2009,50(2):159-166
Genetic susceptibility to HIV infection was previously proven to be influenced by some chemokine receptor polymorphisms clustering
on chromosome 3p21. Here the influence of 5 genetic variants was studied: Δ32CCR5, G(-2459)ACCR5, G190ACCR2, G744ACX3CR1 and C838TCX3CR1. They were screened in a cohort of 168 HIV-1 positive adults [HIV(+) group] and 151 newborns [control group] from northwestern
Poland. PCR-RFLP was performed to screen for the variants (except for A32CCR5 polymorphism, where PCR fragment size was sufficient to identify the alleles) and then electrophoresed on agarose gel to
determine fragment size. Distribution of genotypes and alleles was not significantly different between the groups except for
theCCR5 polymorphisms, with the A32 allele and the (-2459)ACCR5 allele more frequent among neonates than in the HIV(+) group. No Δ32/Δ32 homozygotes were found in the HIV(+) group, but
16.1% were Δ32/wt heterozygotes. In the control group, 1.3% were Δ32/Δ32 homozygotes and 26.0% were Δ32/wt heterozygotes.
Linkage between the chemokine polymorphisms was calculated using the most informative loci for haplotype reconstruction. Haplotypes
containing Δ32 CCR5,190GCCR2 and 744ACX3CR1 were found to be significantly more common in the control group. This suggests an association between these haplotypes and
resistance to HIV-1 infection. 相似文献
128.
129.
Olga Wesołowska Andrzej B. Hendrich Barbara Łania-Pietrzak Jerzy Wiśniewski Joseph Molnar Imre Ocsovszki Krystyna Michalak 《Cellular & molecular biology letters》2009,14(2):199-221
The expression of transmembrane transporter multidrug resistance-associated protein 1 (MRP1) confers the multidrug-resistant
phenotype (MDR) on cancer cells. Since the activity of the other MDR transporter, P-glycoprotein, is sensitive to membrane
perturbation, we aimed to check whether the changes in lipid bilayer properties induced by flavones (apigenin, acacetin) and
flavonols (morin, myricetin) were related to their MRP1 inhibitory activity. All the flavonoids inhibited the efflux of MRP1
fluorescent substrate from human erythrocytes and breast cancer cells. Morin was also found to stimulate the ATPase activity
of erythrocyte ghosts. All flavonoids intercalated into phosphatidylcholine bilayers as judged by differential scanning calorimetry
and fluorescence spectroscopy with the use of two carbocyanine dyes. The model of an intramembrane localization for flavones
and flavonols was proposed. No clear relationship was found between the membrane-perturbing activity of flavonoids and their
potency to inhibit MRP1. We concluded that mechanisms other than perturbation of the lipid phase of membranes were responsible
for inhibition of MRP1 by the flavonoids. 相似文献
130.
Łysek R Schütz C Favre S O'Sullivan AC Pillonel C Krülle T Jung PM Clotet-Codina I Esté JA Vogel P 《Bioorganic & medicinal chemistry》2006,14(18):6255-6282
A solid-phase synthesis of new N-substituted valienamines has been developed and new synthesis of (+/-)-conduramine F-1, (-)-conduramine F-1, and (+)-ent-conduramine F-1 is presented, together with the preparation of N-benzylated conduramines F-1. N-Benzylation of both valienamine and (+)-ent-conduramine F-1 improves their inhibitory activity toward alpha-glucosidases significantly. The additional hydroxymethyl group makes valienamine derivatives more active than their (+)-ent-conduramine F-1 analogues. 相似文献