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101.
Gal Markel Erez Bar-Haim Eran Zahavy Hila Cohen Ofer Cohen Avigdor Shafferman Baruch Velan 《PloS one》2010,5(6)
Background
Francisella tularensis is an intercellular bacterium often causing fatal disease when inhaled. Previous reports have underlined the role of cell-mediated immunity and IFNγ in the host response to Francisella tularensis infection.Methodology/Principal Findings
Here we provide evidence for the involvement of IL-17A in host defense to inhalational tularemia, using a mouse model of intranasal infection with the Live Vaccine Strain (LVS). We demonstrate the kinetics of IL-17A production in lavage fluids of infected lungs and identify the IL-17A-producing lymphocytes as pulmonary γδ and Th17 cells. The peak of IL-17A production appears early during sub-lethal infection, it precedes the peak of immune activation and the nadir of the disease, and then subsides subsequently. Exogenous airway administration of IL-17A or of IL-23 had a limited yet consistent effect of delaying the onset of death from a lethal dose of LVS, implying that IL-17A may be involved in restraining the infection. The protective role for IL-17A was directly demonstrated by in vivo neutralization of IL-17A. Administration of anti IL-17A antibodies concomitantly to a sub-lethal airway infection with 0.1×LD50 resulted in a fatal disease.Conclusion
In summary, these data characterize the involvement and underline the protective key role of the IL-17A axis in the lungs from inhalational tularemia. 相似文献102.
103.
Kristen K. Maul Lucas C. Parra Delanthi Salgado‐Commissariat Douglas Ballon Ofer Tchernichovski Santosh A. Helekar 《Developmental neurobiology》2010,70(1):28-40
Juvenile male zebra finches develop their song by imitation. Females do not sing but are attracted to males' songs. With functional magnetic resonance imaging and event‐related potentials we tested how early auditory experience shapes responses in the auditory forebrain of the adult bird. Adult male birds kept in isolation over the sensitive period for song learning showed no consistency in auditory responses to conspecific songs, calls, and syllables. Thirty seconds of song playback each day over development, which is sufficient to induce song imitation, was also sufficient to shape stimulus‐specific responses. Strikingly, adult females kept in isolation over development showed responses similar to those of males that were exposed to songs. We suggest that early auditory experience with songs may be required to tune perception toward conspecific songs in males, whereas in females song selectivity develops even without prior exposure to song. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2010 相似文献
104.
105.
Hanna J Goldman-Wohl D Hamani Y Avraham I Greenfield C Natanson-Yaron S Prus D Cohen-Daniel L Arnon TI Manaster I Gazit R Yutkin V Benharroch D Porgador A Keshet E Yagel S Mandelboim O 《Nature medicine》2006,12(9):1065-1074
Human CD56(bright) NK cells accumulate in the maternal decidua during pregnancy and are found in direct contact with fetal trophoblasts. Several mechanisms have been proposed to explain the inability of NK cells to kill the semiallogeneic fetal cells. However, the actual functions of decidual NK (dNK) cells during pregnancy are mostly unknown. Here we show that dNK cells, but not peripheral blood-derived NK subsets, regulate trophoblast invasion both in vitro and in vivo by production of the interleukin-8 and interferon-inducible protein-10 chemokines. Furthermore, dNK cells are potent secretors of an array of angiogenic factors and induce vascular growth in the decidua. Notably, such functions are regulated by specific interactions between dNK-activating and dNK-inhibitory receptors and their ligands, uniquely expressed at the fetal-maternal interface. The overall results support a 'peaceful' model for reproductive immunology, in which elements of innate immunity have been incorporated in a constructive manner to support reproductive tissue development. 相似文献
106.
107.
Palty R Ohana E Hershfinkel M Volokita M Elgazar V Beharier O Silverman WF Argaman M Sekler I 《The Journal of biological chemistry》2004,279(24):25234-25240
Sodium-calcium exchangers have long been considered inert with respect to monovalent cations such as lithium, choline, and N-methyl-d-glucamine. A key question that has remained unsolved is how despite this, Li(+) catalyzes calcium exchange in mammalian tissues. Here we report that a Na(+)/Ca(2+) exchanger, NCLX cloned from human cells (known as FLJ22233), is distinct from both known forms of the exchanger, NCX and NCKX in structure and kinetics. Surprisingly, NCLX catalyzes active Li(+)/Ca(2+) exchange, thereby explaining the exchange of these ions in mammalian tissues. The NCLX protein, detected as both 70- and 55-KDa polypeptides, is highly expressed in rat pancreas, skeletal muscle, and stomach. We demonstrate, moreover, that NCLX is a K(+)-independent exchanger that catalyzes Ca(2+) flux at a rate comparable with NCX1 but without promoting Na(+)/Ba(2+) exchange. The activity of NCLX is strongly inhibited by zinc, although it does not transport this cation. NCLX activity is only partially inhibited by the NCX inhibitor, KB-R7943. Our results provide a cogent explanation for a fundamental question. How can Li(+) promote Ca(2+) exchange whereas the known exchangers are inert to Li(+) ions? Identification of this novel member of the Na(+)/Ca(2+) superfamily, with distinct characteristics, including the ability to transport Li(+), may provide an explanation for this phenomenon. 相似文献
108.
Ion channels open and close their pore in a process called gating. On the basis of crystal structures of two voltage-independent K(+) channels, KcsA and MthK, a conformational change for gating has been proposed whereby the inner helix bends at a glycine hinge point (gating hinge) to open the pore and straightens to close it. Here we ask if a similar gating hinge conformational change underlies the mechanics of pore opening of two eukaryotic voltage-dependent K(+) channels, Shaker and BK channels. In the Shaker channel, substitution of the gating hinge glycine with alanine and several other amino acids prevents pore opening, but the ability to open is recovered if a secondary glycine is introduced at an adjacent position. A proline at the gating hinge favors the open state of the Shaker channel as if by preventing inner helix straightening. In BK channels, which have two adjacent glycine residues, opening is significantly hindered in a graded manner with single and double mutations to alanine. These results suggest that K(+) channels, whether ligand- or voltage-dependent, open when the inner helix bends at a conserved glycine gating hinge. 相似文献
109.
Podsiadlo P Komiyama T Fuller RS Blum O 《The Journal of biological chemistry》2004,279(35):36219-36227
Furin, a human subtilisin-related proprotein convertase (SPC), is emerging as an important pharmaceutical target because it processes vital proteins of many aggressive pathogens. Furin inhibitors reported as yet are peptide derivatives and proteins, with the exception of andrographolides, which are natural compounds. Here we report that the small and highly stable compounds M(chelate)Cl(2) (M is copper or zinc) inhibit furin and Kex2, with Cu(TTP)Cl(2) and Zn(TTP)Cl(2) as the most efficient inhibitors. (TTP is 4'-[p-tolyl]-2,2 ':6',2"-terpyridine.) Inhibition is irreversible, competitive with substrate, and affected by substituents on the chelate. The free chelates are not inhibitors. Solvated Zn(2+) is less potent than its complexes. This is true also for copper and Kex2. However, solvated Cu(2+) (k(on) of 25,000 +/- 2,500 s(-1)) is more potent than Cu(TTP)Cl(2) (k(on) = 140 +/- 13 s(-1) and allows recovery of furin activity prior to a second inhibition phase. A mechanism that involves coordination to the catalytic histidine is proposed for all inhibitors. Target specificity is indicated by the fact that these metal chelate inhibitors are much less potent toward Kex2, the yeast homologue of furin. For example, k(on) with Zn(TTP)Cl(2) is 120 +/- 20 s(-1) for furin, but only 1.2 +/- 0.1 s(-1) for Kex2. 相似文献
110.
Hidden messages in the nef gene of human immunodeficiency virus type 1 suggest a novel RNA secondary structure 总被引:1,自引:0,他引:1
The coexistence of multiple codes in the genome of human immunodeficiency virus type 1 (HIV-1) was analyzed. We explored factors constraining the variability of the virus genome primarily in relation to conserved RNA secondary structures overlapping coding sequences, and used a simple combination of algorithms for RNA secondary structure prediction based on the nearest-neighbor thermodynamic rules and a statistical approach. In our previous study, we applied this combination to a non- redundant data set of env nucleotide sequences, confirmed the conservative secondary structure of the rev-responsive element (RRE) and found a new RNA structure in the first conserved (C1) region of the env gene. In this study, we analyzed the variability of putative RNA secondary structures inside the nef gene of HIV-1 by applying these algorithms to a non-redundant data set of 104 nef sequences retrieved from the Los Alamos HIV database, and predicted the existence of a novel functional RNA secondary structure in the β3/β4 regions of nef. The predicted RNA fold in the β3/β4 region of nef appears in two forms with different loop sizes. The loop of the first fold consists of seven nucleotides (positions 494–500), with consensus UCAAGCU appearing in 79% of sequences. The other has a five-base loop (positions 495–499) with consensus CAAGC. The difference in size between these two loops may reflect the difference between respective counterparts in the hairpin recognition. This may also have an adaptive biological significance. 相似文献