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41.
D. Speijer G. R. Manjeri R. Szklarczyk 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2014,369(1646)
Oxygen radical formation in mitochondria is an incompletely understood attribute of eukaryotic cells. Recently, a kinetic model was proposed, in which the ratio between electrons entering the respiratory chain via FADH2 or NADH determines radical formation. During glucose breakdown, the ratio is low; during fatty acid breakdown, the ratio is high (the ratio increasing—asymptotically—with fatty acid length to 0.5, when compared with 0.2 for glucose). Thus, fatty acid oxidation would generate higher levels of radical formation. As a result, breakdown of fatty acids, performed without generation of extra FADH2 in mitochondria, could be beneficial for the cell, especially in the case of long and very long chained ones. This possibly has been a major factor in the evolution of peroxisomes. Increased radical formation, as proposed by the model, can also shed light on the lack of neuronal fatty acid oxidation and tells us about hurdles during early eukaryotic evolution. We specifically focus on extending and discussing the model in light of recent publications and findings. 相似文献
42.
《Bioorganic & medicinal chemistry》2014,22(1):141-147
A series of new sulfonamides was prepared starting from 2-oxo-N′-(4-sulfamoylphenyl)-propanehydrazonoyl chloride, a sulfanilamide derivative, which was reacted with aroylhydrazides, amines, or thiols. A library of derivatives incorporating aroylhydrazone, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl- or 2-(cyanophenyl-methylene)-1,3,4-thiadiazol-3(2H)-yl moieties was thus synthesized. The new compounds were investigated as inhibitors of four α-carbonic anhydrases (CAs, EC 4.2.1.1), the human (h) isoforms hCA I and II, and the bacterial ones recently isolated from the extremophilic bacteria Sulfurihydrogenibium yellostonense (SspCA) and Sulfurihydrogenibium azorense (SazCA). Low nanomolar activity was observed against hCA II (KIs of 0.56–17.1 nM) whereas hCA I was less inhibited by these compounds (KIs of 86.4 nM–32.8 μM). The bacterial CAs were also effectively inhibited by these derivatives (KIs in the range of 0.77–234 nM against SazCA, and of 6.2–89.1 against SspCA, respectively), with several low nanomolar/subnanomolar inhibitors detected against both of them. As SspCA and SazCA are among the most thermostable and catalytically active CAs, it is of interest to find modulators of their activity for potential biotechnologic applications. 相似文献
43.
A recent examination of color vision in the ringtail lemur produced evidence that these prosimians could make color discriminations consistent with a diagnosis of trichromatic color vision. However, it was unclear if this behavior reflected the presence of three classes of cone or whether lemurs might be able to utilize signals from rods in conjunction with those from only two classes of cone. To resolve that issue, spectral sensitivity functions were obtained from ringtail lemurs (Lemur catta) and brown lemurs (Eulemur fulvus) using a noninvasive electrophysiological procedure, electroretinographic flicker photometry. Results from experiments involving chromatic adaptation indicate that these lemurs routinely have only a single class of cone photopigment in the middle to long wavelengths (peak sensitivity of about 545 nm); they also have a short-wavelengthsensitive cone pigment with peak of about 437 nm. The earlier behavioral results are suggested to have resulted from the ability of lemurs to jointly utilize signals from rods and cones. The cone pigment complements of these lemurs differ distinctly from those seen among the anthropoids. © 1993 Wiley-Liss, Inc. 相似文献
44.
Comparative studies of mammalian lysozymes and their genes have contributed to knowledge of how new functions arise during evolution. The recruitment of lysozymes for functioning in the stomach fluid of ruminants has occurred in response to selection pressures that are partly known and on a time-scale that is known. A semiquantitative analysis of adaptive evolution is thus made possible by the ruminant lysozyme system. Large-scale production of lysozyme by the stomach lining entailed gene duplication as well as a change in gene expression. Remoulding of the lysozyme for working and lasting in the stomach fluid involved accelerated amino acid replacements, which may have been facilitated by intergenic recombination. The possibility that multigene families can accelerate adaptive evolution, by virtue of their capacity for bringing together functionally coupled substitutions, receives emphasis in this review. 相似文献
45.
Mitochondrial dehydrogenase activity was measured in seven taxa of Tetrahymena (T. pyriformis G1, T. hegewishi, T. malaccensis, T. pigmentosa, T. shapiro, T. thermophila CU-399, T. thermophila MS-1). Enzyme activity was different in the taxa investigated. Insulin reduced enzyme activity in six of the seven taxa studied. The duration of activity reduction was relatively long (5–10 min.) in most of the cases, and in T. hegewishi this lasted up to the end of the measurements (30 min.). There was no interrelation between the basic dehydrogenase activity of the taxon and the effect of insulin. There was also no correlation between the degree of relationship (of the taxa) and the dehydrogenase profile after insulin treatment. 相似文献
46.
The 231-residue capsid (CA) protein of human immunodeficiency virus type 1 (HIV-1) spontaneously self-assembles into tubes with a hexagonal lattice that is believed to mimic the surface lattice of conical capsid cores within intact virions. We report the results of solid-state nuclear magnetic resonance (NMR) measurements on HIV-1 CA tubes that provide new information regarding changes in molecular structure that accompany CA self-assembly, local dynamics within CA tubes, and possible mechanisms for the generation of lattice curvature. This information is contained in site-specific assignments of signals in two- and three-dimensional solid-state NMR spectra, conformation-dependent 15N and 13C NMR chemical shifts, detection of highly dynamic residues under solution NMR conditions, measurements of local variations in transverse spin relaxation rates of amide 1H nuclei, and quantitative measurements of site-specific 15N–15N dipole–dipole couplings. Our data show that most of the CA sequence is conformationally ordered and relatively rigid in tubular assemblies and that structures of the N-terminal domain (NTD) and the C-terminal domain (CTD) observed in solution are largely retained. However, specific segments, including the N-terminal β-hairpin, the cyclophilin A binding loop, the inter-domain linker, segments involved in intermolecular NTD–CTD interactions, and the C-terminal tail, have substantial static or dynamical disorder in tubular assemblies. Other segments, including the 310-helical segment in CTD, undergo clear conformational changes. Structural variations associated with curvature of the CA lattice appear to be localized in the inter-domain linker and intermolecular NTD–CTD interface, while structural variations within NTD hexamers, around local 3-fold symmetry axes, and in CTD–CTD dimerization interfaces are less significant. 相似文献
47.
Hyun-Jin Kang Tuong Vy Thi Le Kyungmin Kim Jeonghwan Hur Kyeong Kyu Kim Hyun-Ju Park 《Journal of molecular biology》2014
Both G-quadruplex and Z-DNA can be formed in G-rich and repetitive sequences on genome, and their formation and biological functions are controlled by specific proteins. Z-DNA binding proteins, such as human ADAR1, have a highly conserved Z-DNA binding domain having selective affinity to Z-DNA. Here, our study identifies the Z-DNA binding domain of human ADAR1 (hZαADAR1) as a novel G-quadruplex binding protein that recognizes c-myc promoter G-quadruplex formed in NHEIII1 region and represses the gene expression. An electrophoretic migration shift assay shows the binding of hZαADAR1 to the intramolecular c-myc promoter G-quadruplex-forming DNA oligomer. To corroborate the binding of hZαADAR1 to the G-quadruplex, we conducted CD and NMR chemical shift perturbation analyses. CD results indicate that hZαADAR1 stabilizes the parallel-stranded conformation of the c-myc G-quadruplex. The NMR chemical shift perturbation data reveal that the G-quadruplex binding region in hZαADAR1 was almost identical with the Z-DNA binding region. Finally, promoter assay and Western blot analysis show that hZαADAR1 suppresses the c-myc expression promoted by NHEIII1 region containing the G-quadruplex-forming sequence. This finding suggests a novel function of Z-DNA binding protein as a regulator of G-quadruplex-mediated gene expression. 相似文献
48.
Justyna McIntyre Mary P. McLenigan Ekaterina G. Frank Xiaoxia Dai Wei Yang Yinsheng Wang Roger Woodgate 《The Journal of biological chemistry》2015,290(45):27332-27344
Human DNA polymerases (pols) η and ι are Y-family DNA polymerase paralogs that facilitate translesion synthesis past damaged DNA. Both polη and polι can be monoubiquitinated in vivo. Polη has been shown to be ubiquitinated at one primary site. When this site is unavailable, three nearby lysines may become ubiquitinated. In contrast, mass spectrometry analysis of monoubiquitinated polι revealed that it is ubiquitinated at over 27 unique sites. Many of these sites are localized in different functional domains of the protein, including the catalytic polymerase domain, the proliferating cell nuclear antigen-interacting region, the Rev1-interacting region, and its ubiquitin binding motifs UBM1 and UBM2. Polι monoubiquitination remains unchanged after cells are exposed to DNA-damaging agents such as UV light (generating UV photoproducts), ethyl methanesulfonate (generating alkylation damage), mitomycin C (generating interstrand cross-links), or potassium bromate (generating direct oxidative DNA damage). However, when exposed to naphthoquinones, such as menadione and plumbagin, which cause indirect oxidative damage through mitochondrial dysfunction, polι becomes transiently polyubiquitinated via Lys11- and Lys48-linked chains of ubiquitin and subsequently targeted for degradation. Polyubiquitination does not occur as a direct result of the perturbation of the redox cycle as no polyubiquitination was observed after treatment with rotenone or antimycin A, which both inhibit mitochondrial electron transport. Interestingly, polyubiquitination was observed after the inhibition of the lysine acetyltransferase KATB3/p300. We hypothesize that the formation of polyubiquitination chains attached to polι occurs via the interplay between lysine acetylation and ubiquitination of ubiquitin itself at Lys11 and Lys48 rather than oxidative damage per se. 相似文献
49.
Karlheinz Grillitsch Pablo Tarazona Lisa Klug Tamara Wriessnegger Günther Zellnig Erich Leitner Ivo Feussner Günther Daum 《生物化学与生物物理学报:生物膜》2014
Despite similarities of cellular membranes in all eukaryotes, every compartment displays characteristic and often unique features which are important for the functions of the specific organelles. In the present study, we biochemically characterized the plasma membrane of the methylotrophic yeast Pichia pastoris with emphasis on the lipids which form the matrix of this compartment. Prerequisite for this effort was the design of a standardized and reliable isolation protocol of the plasma membrane at high purity. Analysis of isolated plasma membrane samples from P. pastoris revealed an increase of phosphatidylserine and a decrease of phosphatidylcholine compared to bulk membranes. The amount of saturated fatty acids in the plasma membrane was higher than in total cell extracts. Ergosterol, the final product of the yeast sterol biosynthetic pathway, was found to be enriched in plasma membrane fractions, although markedly lower than in Saccharomyces cerevisiae. A further characteristic feature of the plasma membrane from P. pastoris was the enrichment of inositol phosphorylceramides over neutral sphingolipids, which accumulated in internal membranes. The detailed analysis of the P. pastoris plasma membrane is discussed in the light of cell biological features of this microorganism especially as a microbial cell factory for heterologous protein production. 相似文献
50.