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41.
42.
Strobl JS Seibert CW Li Y Nagarkatti R Mitchell SM Rosypal AC Rathore D Lindsay DS 《The Journal of parasitology》2009,95(1):215-223
We searched the National Cancer Institute (NCI) compound library for structures related to the antitumor quinoline NSC3852 (5-nitroso-8-quinolinol) and used a computer algorithm to predict the antiprotozoan activity for each of 13 structures. Half of these compounds inhibited Toxoplasma gondii tachyzoite propagation in human fibroblasts at =1 muM. The active compounds comprise a series of low-molecular-weight quinolines bearing nitrogen substituents in the ring-5 position. NSC3852 (EC(50) 80 nM) and NSC74949 (EC(50) 646 nM) were the most potent. NSC3852 also inhibited Plasmodium falciparum growth in human red blood cells (EC(50) 1.3 muM). To investigate the mechanism for NSC3852's anti-T. gondii activity, we used chemiluminescence assays to detect reactive oxygen species (ROS) formation in freshly isolated tachyzoites and in infected host cells; the absence of ROS generation by NSC3852 in these assays indicated NSC3852 does not redox cycle in T. gondii. Inhibitors of enzyme sources of free radicals such as superoxide anion, nitric oxide (NO), and their reaction product peroxynitrite did not interfere with the anti-T. gondii activity of NSC3852. However, inhibition of T. gondii tachyzoite propagation by NSC3852 involved redox reactions because tachyzoites were protected from NSC3852 by inclusion of the cell permeant superoxide dismutase mimetic, MnTMPyP, or N-acetylcysteine in the culture medium. We conclude that the Prediction of Activity Spectra for Substances (PASS) computer program is useful in finding new compounds that inhibit T. gondii tachyzoites in vitro and that NSC3852 is a potent T. gondii inhibitor that acts by indirect generation of oxidative stress in T. gondii. 相似文献
43.
44.
Background
It is hypothesized that one of the mechanisms promoting diversification in cichlid fishes in the African Great Lakes has been the well-documented pattern of philopatry along shoreline habitats leading to high levels of genetic isolation among populations. However lake habitats are not the only centers of cichlid biodiversity - certain African rivers also contain large numbers of narrowly endemic species. Patterns of isolation and divergence in these systems have tended to be overlooked and are not well understood. 相似文献45.
Andrea LJ Marschall Frank N Single Katrin Schlarmann Andreas Bosio Nina Strebe Joop van den Heuvel André Frenzel Stefan Dübel 《MABS-AUSTIN》2014,6(6):1394-1401
Functional knockdowns mediated by endoplasmatic reticulum-retained antibodies (ER intrabodies) are a promising tool for research because they allow functional interference on the protein level. We demonstrate for the first time that ER intrabodies can induce a knock-down phenotype in mice. Surface VCAM1 was suppressed in bone marrow of heterozygous and homozygous ER intrabody mice (iER-VCAM1 mice). iER-VCAM1 mice did not have a lethal phenotype, in contrast to the constitutive knockout of VCAM1, but adult mice exhibited physiological effects in the form of aberrant distribution of immature B-cells in blood and bone marrow. The capability to regulate knock-down strength may spark a new approach for the functional study of membrane and plasma proteins, which may especially be valuable for generating mouse models that more closely resemble disease states than classic knockouts do. 相似文献
46.
Background
Elucidation of the communal behavior of microbes in mixed species biofilms may have a major impact on understanding infectious diseases and for the therapeutics. Although, the structure and the properties of monospecies biofilms and their role in disease have been extensively studied during the last decade, the interactions within mixed biofilms consisting of bacteria and fungi such as Candida spp. have not been illustrated in depth. Hence, the aim of this study was to evaluate the interspecies interactions of Pseudomonas aeruginosa and six different species of Candida comprising C. albicans, C. glabrata, C. krusei, C. tropicalis, C. parapsilosis, and C. dubliniensis in dual species biofilm development. 相似文献47.
48.
Compensatory substitutions and the evolution of the mitochondrial 12S rRNA gene in mammals 总被引:5,自引:2,他引:3
12S ribosomal RNA (rRNA) gene sequences from a suite of mammalian taxa (13
placentals, 4 marsupials, 1 monotreme), for which phylogenetic
relationships are well established based on independent criteria, were
employed to study the evolution of this gene. Phylogenetic analysis of 12S
sequences produces a phylogeny that agrees with expectations. Base
composition provides evidence for directional symmetrical substitution
pressure in loops; in stems, base composition is much more even. Rates of
nucleotide substitution are lower in stems than loops. Patterns of
nucleotide substitution show an overall preference for transitions over
transversions, with this difference more profound in stems than loops.
Among different transversion pathways, there is a wide range of
transformation frequencies. An analysis of compensatory substitutions shows
that there is strong evidence for their occurrence and that a weighting
factor of 0.61 should be applied in phylogenetic analyses to account for
the dependence of mutations at stem positions relative to positions where
changes are independent. Among stem variables (i.e., stem length,
interaction distance, substitution rates, G+C content, and the percentage
of bases that are paired), several significant correlations were
discovered, but stem length and interaction distance are uncorrelated with
other variables.
相似文献
49.
R L Geller M J Smyth S L Strobl F H Bach F W Ruscetti D L Longo A C Ochoa 《Journal of immunology (Baltimore, Md. : 1950)》1991,146(10):3280-3288
CD4+ and CD8+ T cells do not develop significant lymphokine-activated killer (LAK) activity when PBL are cultured with IL-2 or even when they are activated with a T cell stimulus such as OKT3 mAb. The possibility that a T cell regulatory mechanism prevents the development of LAK activity by CD4+ or CD8+ cells in OKT3 mAb and IL-2 cultures was tested by depleting CD8+ or CD4+ cells from PBL before stimulation with OKT3 and IL-2. Under these conditions, the remaining CD4+ and CD8+ cells were able to generate non-MHC-restricted lysis of NK-resistant tumor targets. Our data suggested that a regulatory signal was present in the culture to prevent the development of lytic function by T cells. T cells removed from the PBL cultures were, upon culture with IL-2, able to generate high LAK activity, suggesting that inhibition of the CD4+ or CD8+ T cell-mediated LAK activity was an active ongoing process, which blocked the lysis at the level of the activated cell and not the precursor cell. Mixing experiments demonstrated that the CD4+ or the CD8+ cells isolated from the PBL cultures were able to inhibit the development of lytic function in the CD4-depleted and CD8-depleted cultures. Transforming growth factor-beta (TGF-beta) has been shown to block LAK activity of NK cells in IL-2-stimulated cultures. When TGF-beta was added to CD4(+)- or CD8(+)-depleted cultures, it also inhibited LAK activity of T cells in a dose-dependent fashion, without interfering with T cell growth. Lytic activity returned to activated levels when TGF-beta was removed from the culture medium, thereby demonstrating the reversibility of TGF-beta inhibition. 相似文献
50.
The restriction enzymes FnuDII and AccII are isoschizomers of the DNA sequence 5-CGCG-3. We have determined that 5-methylcytidine at either cytidine position in this recognition sequence inhibits DNA cleavage by FnuDII and AccII. A third isoschizomer, ThaI was previously shown to exhibit an identical methylation sensitivity. It is remarkable that 3 restriction enzymes derived from diverse microbiological sources exhibit this identical methylation sensitivity.Abbreviations bp
base pair(s)
- mc
5-methylcytidine
- Tris-borate buffer
89 mM Tris-base, 89 mM boric acid, 2.5 mM EDTA, pH 8.3 相似文献