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131.
Tao R Wang L Han R Wang T Ye Q Honjo T Murphy TL Murphy KM Hancock WW 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(9):5774-5782
Although fully MHC-mismatched murine cardiac allografts are rapidly rejected, allografts mismatched at only MHC class I or class II alleles survive long term; the immunologic basis for the long-term survival of MHC class I- or II-mismatched allografts is unknown. We examined the roles of two recently described inhibitory receptors, B and T lymphocyte attenuator (BTLA) and programmed death-1 (PD-1), in the survival of partially or fully MHC-mismatched allografts using gene-deficient recipients as well as through use of blocking mAbs in wild-type hosts. Partially MHC-mismatched allografts showed strong induction of BTLA, but not PD-1 mRNA and survived long term in wild-type recipients, whereas targeting of BTLA or its ligand, herpesvirus entry mediator, but not PD-1, prompted their rapid rejection. By contrast, fully MHC-mismatched cardiac allografts were acutely rejected in wild-type recipients despite the induction of both BTLA and PD-1. Targeting of PD-1 in several fully MHC-mismatched models accelerated rejection, whereas targeting of BTLA unexpectedly enhanced PD-1 induction by alloreactive CD4 and CD8 T cells and prolonged allograft survival. In vitro studies using allogeneic dendritic cells and T cells showed that at low levels of T cell activation, BTLA expression was primarily induced, but that with increasing degrees of T cell activation, the expression of PD-1 was strongly up-regulated. These data suggest that BTLA and PD-1 exert distinct inhibitory actions in vivo, with the BTLA/herpesvirus entry mediator pathway appearing to dominate in regulating responses against a restricted degree of allogeneic mismatch. 相似文献
132.
Matsumoto T Wakabayashi K Kobayashi T Kamata K 《Canadian journal of physiology and pharmacology》2004,82(3):175-182
We used the partial protection exerted by suitable dosages of nicotinamide against the beta-cytotoxic effect of streptozotocin (STZ) to create an experimental diabetic syndrome in adult rats that appears closer to type II diabetes mellitus than other available animal models. The dosage of 230 mg/kg of nicotinamide given intraperitoneally 15 min before STZ administration (65 mg/kg i.v.) yielded animals with hyperglycemia (187.8 +/- 17.8 vs. 103.8 +/- 2.8 mg/dL in controls; P < 0.001) and preservation of plasma insulin levels. This study assessed the relationship between endothelial dysfunction and agonist-induced contractile responses in such rats. In the thoracic aorta, the acetylcholine (ACh) induced relaxation was significantly reduced and the noradrenaline (NA) induced contractile response was significantly increased in diabetic rats compared with age-matched control rats. In the superior mesenteric artery, the ACh-induced relaxation was similar in magnitude between diabetic and age-matched control rats; however, the ACh-induced endothelium-derived hyperpolarizing factor (EDHF) type relaxation was significantly weaker in diabetic rats than in the controls. The phenylephrine (PE) induced contractile response was not different between the two groups. The plasma concentration of NOx (NO2- + NO3-) was significantly lower in diabetic rats than in control rats. We conclude that vasomotor activities in conduit arteries are impaired in this type II diabetes model. 相似文献
133.
T cells from TCR transgenic mice, expressing receptors specific for an allogeneic MHC class I peptide, were used to track T cell activation and migration in normal adoptive recipients that were subsequently transplanted with heterotopic hearts that were syngeneic except for a transgenic MHC class I antigen. T cells rapidly disappeared from the blood into the lymphoid tissues where they were activated within one day after transplantation. T cells initially formed discrete clusters in the spleen and lymph nodes. After proliferating for 2-4 days in lymphoid tissues, T cells reappeared in the blood and migrated to the heart and the intestines. The T cells underwent another round of proliferation in the heart, but not the intestines, and induced cardiac rejection uniformly on 6 day. 相似文献
134.
135.
Fujikura J Hosoda K Iwakura H Tomita T Noguchi M Masuzaki H Tanigaki K Yabe D Honjo T Nakao K 《Cell metabolism》2006,3(1):59-65
To investigate the precise role of Notch/Rbp-j signaling in the pancreas, we inactivated Rbp-j by crossing Rbp-j floxed mice with Pdx.cre or Rip.cre transgenic mice. The loss of Rbp-j at the initial stage of pancreatic development induced accelerated alpha and PP cell differentiation and a concomitant decrease in the number of Neurogenin3 (Ngn3)-positive cells at E11.5. Then at E15, elongated tubular structures expressing ductal cell markers were evident; however, differentiation of acinar and all types of endocrine cells were reduced. During later embryonic stages, compensatory acinar cell differentiation was observed. The resultant mice exhibited insulin-deficient diabetes with both endocrine and exocrine pancreatic hypoplasia. In contrast, the loss of Rbp-j specifically in beta cells did not affect beta cell number and function. Thus, our analyses indicate that Notch/Rbp-j signaling prevents premature differentiation of pancreatic progenitor cells into endocrine and ductal cells during early development of the pancreas. 相似文献
136.
Sou Nagasoe Dae-Il Kim Yohei Shimasaki Yuji Oshima Mineo Yamaguchi Tsuneo Honjo 《Harmful algae》2006,5(1):20-25
The effects of temperature, salinity and irradiance on the growth of the red tide dinoflagellate Gyrodinium instriatum Freudenthal et Lee were examined in the laboratory. Exposed to 45 different combinations of temperature (10–30 °C) and salinity (0–40) under saturating irradiance, G. instriatum exhibited its maximum growth rate of 0.7 divisions/day at a combination of 25 °C and a salinity of 30. Optimum growth rates (>0.5 divisions/day) were observed at temperatures ranging from 20 to 30 °C and at salinities from 10 to 35. The organism could not grow at ≤10 °C. In addition, G. instriatum burst at a salinity of 0 at all temperatures, but grew at a salinity of 5 at temperatures between 20 and 25 °C. It is noteworthy that G. instriatum is a euryhaline organism that can live under extremely low salinity. Factorial analysis revealed that the contributions of temperature and salinity to its growth of the organism were almost equal. The irradiance at the light compensation point (I0) was 10.6 μmol/(m2 s) and the saturated irradiance for growth (Is) was 70 μmol/(m2 s), which was lower than Is for several other harmful dinoflagellates (90–110 μmol/(m2 s)). 相似文献
137.
Genetic variations in the chloroplast genome and phylogenetic clustering of Lycoris species 总被引:2,自引:0,他引:2
The genus Lycoris of Amaryllidaceae comprises approximately 20 species that are distributed only in the moist warm temperate woodlands of eastern Asia. The objectives of this study were: (1) to clarify the phylogeny of the Lycoris species by using the definitive DNA sequencing method and (2) to examine the possible maternal donor of the hybrid origin Lycoris species and the Japanese triploid strains of Lycoris radiata var. radiata. The nucleotide sequence of the maturase K (matK) gene and the noncoding intergenic spacer (IGS) between the atpB and rbcL genes in the chloroplast genome were determined in a total of 27 strains of 11 species of the genus Lycoris. Variation among taxa was mainly due to nucleotide substitution, although deletions and an insertion were found in the IGS. For two chloroplast regions, the phylogenetic trees showed essentially similar topology, indicating the existence of four clades, I, II, III, and IV. For all the species except L. radiata, intraspecific variation was smaller than interspecific variation. For L. radiata, triploid strains were divided into clades I and II, and diploid strains were divided into clades I and IV. This implies that the diploid species of L. radiata var. pumila is a probable ancestral species. The clustering indicated that the chloroplast genome has not evolved in parallel with the karyotype in genus Lycoris. Regarding the hybrid origin species, the maternal parents of L. squamigara, L. albiflora and L. rosea were revealed to be L. longituba, L. radiata and L. radiata var pumila, respectively. We also suggest that a diploid strain of L. radiata var. pumila in clade I might be a candidate of the maternal donor of the Japanese triploid strains. A possible model of the maternal donor of Lycoris species is proposed. 相似文献
138.
Rejuvenating exhausted T cells during chronic viral infection 总被引:6,自引:0,他引:6
In a recent paper in Nature, show that the immunoreceptor PD-1 is upregulated by "exhausted" T cells during the chronic phase of viral infection in mice. Remarkably, blocking the interaction between PD-1 and its ligand, PD-L1, reactivates these T cells and reduces viral load. 相似文献
139.
Kato L Stanlie A Begum NA Kobayashi M Aida M Honjo T 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(8):3559-3566
An ortholog of activation-induced cytidine deaminase (AID) was, evolutionarily, the first enzyme to generate acquired immune diversity by catalyzing gene conversion and probably somatic hypermutation (SHM). AID began to mediate class switch recombination (CSR) only after the evolution of frogs. Recent studies revealed that the mechanisms for generating immune and genetic diversity share several critical features. Meiotic recombination, V(D)J recombination, CSR, and SHM all require H3K4 trimethyl histone modification to specify the target DNA. Genetic instability related to dinucleotide or triplet repeats depends on DNA cleavage by topoisomerase 1, which also initiates DNA cleavage in both SHM and CSR. These similarities suggest that AID hijacked the basic mechanism for genome instability when AID evolved in jawless fish. Thus, the risk of introducing genome instability into nonimmunoglobulin loci is unavoidable but tolerable compared with the advantage conferred on the host of being protected against pathogens by the enormous Ig diversification. 相似文献
140.
Miyazaki T Takenaka T Inoue T Sato M Miyajima Y Nodera M Hanyu M Ohno Y Shibazaki S Suzuki H 《Biological trace element research》2012,145(3):375-381
Zinc deficiency leads to decreased cellular immune responses. The overproduction of nitrogen species derived from inducible
nitric oxide synthase (iNOS), its enzyme, and interleukine-1 beta (IL-1β), and inflammatory cytokine have been implicated
in immune responses. The goal of this study was to investigate the effects of lipopolysaccharide (LPS)-induced changes in
NO metabolites, iNOS, and IL-1β protein expression in the lungs of zinc-deficient rats. Male Sprague–Dawley rats (body weight,
100 g) were divided into two groups and were fed either a zinc-deficient diet (ZnD) or a zinc-containing diet (Cont). After
4 weeks on these diets, rats received a 10-mg/kg dose of LPS injected via the tail vein and were then maintained for an additional
72 h. To determine total NO concentrations in the blood, serum zinc concentration, iNOS protein expression, IL-1β, and iNOS
immunohistochemistry, blood and lung samples were obtained at pre-LPS injection, 5, 24, and 72 h after injection. Total NO
levels were significantly increased at 5, at 24, and at 72 h after LPS injection compared with pre-LPS injection level in
ZnD group; significant changes in total NO levels was elevated at 5 h from at pre-LPS level but not significant changes from
basal level at 24 and 72 h in the control group. Based on western blot analyses and immunohistochemistry, clear bands indicating
iNOS and IL-1β protein expression and iNOS antibody-stained inflammatory cells were detected at 5 and 24 h in the ZnD group
and 5 h in the Cont group, not observed at 24 and 72 h in the control group. These results suggest that zinc deficiency induces
overexpression of iNOS and IL-1β proteins from inflammatory cells around the alveolar blood vessels, resulting in overproduction
of total NO and persisted inflammatory response in the zinc-deficient rat lung. Taken together, overexpression of LPS-induced
iNOS, overproduction of iNOS-derived NO, and overexpression of IL-1β may induce nitrosative and oxidative stresses in the
lung, and these stresses may be involved low immunity of zinc deficiency states. 相似文献