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41.
42.
Xabier Agirrezabala Ekaterina Samatova Meline Macher Marija Liutkute Manisankar Maiti David GilCarton Jiri Novacek Mikel Valle Marina V Rodnina 《The EMBO journal》2022,41(4)
Cellular proteins begin to fold as they emerge from the ribosome. The folding landscape of nascent chains is not only shaped by their amino acid sequence but also by the interactions with the ribosome. Here, we combine biophysical methods with cryo‐EM structure determination to show that folding of a β‐barrel protein begins with formation of a dynamic α‐helix inside the ribosome. As the growing peptide reaches the end of the tunnel, the N‐terminal part of the nascent chain refolds to a β‐hairpin structure that remains dynamic until its release from the ribosome. Contacts with the ribosome and structure of the peptidyl transferase center depend on nascent chain conformation. These results indicate that proteins may start out as α‐helices inside the tunnel and switch into their native folds only as they emerge from the ribosome. Moreover, the correlation of nascent chain conformations with reorientation of key residues of the ribosomal peptidyl‐transferase center suggest that protein folding could modulate ribosome activity. 相似文献
43.
Marina P. Slezina Ekaterina A. Istomina Ekaterina V. Kulakovskaya Tatiana N. Abashina Tatyana I. Odintsova 《Current issues in molecular biology》2021,43(3):1226
Plant cysteine-rich peptides (CRPs) represent a diverse group of molecules involved in different aspects of plant physiology. Antimicrobial peptides, which directly suppress the growth of pathogens, are regarded as promising templates for the development of next-generation pharmaceuticals and ecologically friendly plant disease control agents. Their oligopeptide fragments are even more promising because of their low production costs. The goal of this work was to explore the antimicrobial activity of nine short peptides derived from the γ-core-containing regions of tomato CRPs against important plant and human pathogens. We discovered antimicrobial activity in peptides derived from the defensin-like peptides, snakins, and MEG, which demonstrates the direct involvement of these CRPs in defense reactions in tomato. The CRP-derived short peptides appeared particularly active against the gram-positive bacterium Clavibacter michiganensis, which causes bacterial wilt—opening up new possibilities for their use in agriculture to control this dangerous disease. Furthermore, high inhibitory potency of short oligopeptides was demonstrated against the yeast Cryptococcus neoformans, which causes serious diseases in humans, making these peptide molecules promising candidates for the development of next-generation pharmaceuticals. Studies of the mode of action of the two most active peptides indicate fungal membrane permeabilization as a mechanism of antimicrobial action. 相似文献
44.
Ekaterina V. Madyarova Renat V. Adelshin Mariya D. Dimova Denis V. Axenov-Gribanov Yulia A. Lubyaga Maxim A. Timofeyev 《PloS one》2015,10(6)
At present, approximately 187 genera and over 1300 species of Microsporidia have been described, among which almost half infect aquatic species and approximately 50 genera potentially infect aquatic arthropods. Lake Baikal is the deepest and one of the oldest lakes in the world, and it has a rich endemic fauna with a predominance of arthropods. Among the arthropods living in this lake, amphipods (Crustacea) are the most dominant group and are represented by more than 350 endemic species. Baikalian amphipods inhabit almost all depths and all types of substrates. The age and geographical isolation of this group creates excellent opportunities for studying the diversity, evolution and genetics of host-parasite relationships. However, despite more than 150 years of study, data investigating the microsporidia of Lake Baikal remain incomplete. In this study, we used molecular genetic analyses to detect microsporidia in the hemolymph of several endemic species of amphipods from Lake Baikal. We provide the first evidence that microsporidian species belonging to three genera (Microsporidium, Dictyocoela and Nosema) are present in the hemolymph of Baikalian endemic amphipods. In the hemolymph of Eulimnogammarus verrucosus, we detected SSU rDNA of microsporidia belonging to the genus Nozema. In the hemolymph of Pallasea cancellous, we found the DNA of Microsporidium sp. similar to that in other Baikalian endemic amphipods; Dictyocoela sp. was found in the hemolymph of Eulimnogammarus marituji and Acanthogammarus lappaceus longispinus. 相似文献
45.
Proudfoot M Kuznetsova E Brown G Rao NN Kitagawa M Mori H Savchenko A Yakunin AF 《The Journal of biological chemistry》2004,279(52):54687-54694
To find proteins with nucleotidase activity in Escherichia coli, purified unknown proteins were screened for the presence of phosphatase activity using the general phosphatase substrate p-nitrophenyl phosphate. Proteins exhibiting catalytic activity were then assayed for nucleotidase activity against various nucleotides. These screens identified the presence of nucleotidase activity in three uncharacterized E. coli proteins, SurE, YfbR, and YjjG, that belong to different enzyme superfamilies: SurE-like family, HD domain family (YfbR), and haloacid dehalogenase (HAD)-like superfamily (YjjG). The phosphatase activity of these proteins had a neutral pH optimum (pH 7.0-8.0) and was strictly dependent on the presence of divalent metal cations (SurE: Mn(2+) > Co(2+) > Ni(2+) > Mg(2+); YfbR: Co(2+) > Mn(2+) > Cu(2+); YjjG: Mg(2+) > Mn(2+) > Co(2+)). Further biochemical characterization of SurE revealed that it has a broad substrate specificity and can dephosphorylate various ribo- and deoxyribonucleoside 5'-monophosphates and ribonucleoside 3'-monophosphates with highest affinity to 3'-AMP. SurE also hydrolyzed polyphosphate (exopolyphosphatase activity) with the preference for short-chain-length substrates (P(20-25)). YfbR was strictly specific to deoxyribonucleoside 5'-monophosphates, whereas YjjG showed narrow specificity to 5'-dTMP, 5'-dUMP, and 5'-UMP. The three enzymes also exhibited different sensitivities to inhibition by various nucleoside di- and triphosphates: YfbR was equally sensitive to both di- and triphosphates, SurE was inhibited only by triphosphates, and YjjG was insensitive to these effectors. The differences in their sensitivities to nucleotides and their varied substrate specificities suggest that these enzymes play unique functions in the intracellular nucleotide metabolism in E. coli. 相似文献
46.
Passive antibody therapy for infectious diseases 总被引:5,自引:0,他引:5
Antibody-based therapies are currently undergoing a renaissance. After being developed and then largely abandoned in the twentieth century, many antibody preparations are now in clinical use. However, most of the reagents that are available target non-infectious diseases. Interest in using antibodies to treat infectious diseases is now being fuelled by the wide dissemination of drug-resistant microorganisms, the emergence of new microorganisms, the relative inefficacy of antimicrobial drugs in immunocompromised hosts and the fact that antibody-based therapies are the only means to provide immediate immunity against biological weapons. Given the need for new antimicrobial therapies and many recent technological advances in the field of immunoglobulin research, there is considerable optimism regarding renewed applications of antibody-based therapy for the prevention and treatment of infectious diseases. 相似文献
47.
Mikko Oivanen Ekaterina V. Efimtseva Sergey N. Mikhailov 《Nucleosides, nucleotides & nucleic acids》2013,32(8):1325-1331
Abstract The first-order rate constants for hydrolysis of 3′-C-methyluridylyl(2′,5′)- and -(3′,5′)adenosine and the corresponding native dinucleoside monophosphates (2′,5′- and 3′,5′-UpA) have been determined as a function of hydroxide-ion concentration (0.025 - 7 M) at 25°C. In addition to the effects on the hydrolytic stability of the compounds, the effects of the 3′-C-methyl substitution on the kinetically determined pK a values for the sugar hydroxyls of the undine moiety are discussed. 相似文献
48.
Ekaterina V. Efimtseva Lubov S. Victorova Andrei A. Rodionov Boris S. Ermolinsky Marina V. Fomitcheva Vera L. Tunitskaya 《Nucleosides, nucleotides & nucleic acids》2013,32(9-11):1681-1684
Abstract A high yield synthesis of different O-ribofuranosylnucleosides has been achieved. Kinetics of the acid-catalysed hydrolysis of disaccharide nucleosides has been studied. Chemical and enzymatic incorporation of 2′-O-ribofuranosyl-nucleoside residue into oligonucleotides was investigated. 相似文献
49.
Rostislav A. Petrov Svetlana Yu. Maklakova Yan A. Ivanenkov Stanislav A. Petrov Olga V. Sergeeva Emil Yu. Yamansarov Irina V. Saltykova Igor I. Kireev Irina B. Alieva Ekaterina V. Deyneka Alina A. Sofronova Anastasiia V. Aladinskaia Alexandre V. Trofimenko Renat S. Yamidanov Sergey V. Kovalev Victor E. Kotelianski Timofey S. Zatsepin Elena K. Beloglazkina Alexander G. Majouga 《Bioorganic & medicinal chemistry letters》2018,28(3):382-387
Asialoglycoprotein receptor (ASGP-R) is a promising biological target for drug delivery into hepatoma cells. Nevertheless, there are only few examples of small-molecule conjugates of ASGP-R selective ligand equipped by a therapeutic agent for the treatment of hepatocellular carcinoma (HCC). In the present work, we describe a convenient and versatile synthetic approach to novel mono- and multivalent drug-conjugates containing N-acetyl-2-deoxy-2-aminogalactopyranose and anticancer drug – paclitaxel (PTX). Several molecules have demonstrated high affinity towards ASGP-R and good stability under physiological conditions, significant in vitro anticancer activity comparable to PTX, as well as good internalization via ASGP-R-mediated endocytosis. Therefore, the conjugates with the highest potency can be regarded as a promising therapeutic option against HCC. 相似文献
50.