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991.
In an effort to define the mechanism underlying the host immune downregulation inherent to Trichinella spiralis infection, we compared the levels of Th1, Th2, and regulatory cytokines and CD4+CD25+ forkhead box P3 (FoxP3)+ T (Treg) cell recruitment, as well as cellular pathology in the airway between T. spiralis infected and uninfected asthma-induced mice. After the induction of allergic airway inflammation, we noted influxes of inflammatory cells into the peribronchial tree. However, in the T. spiralis infection groups, cellular infiltration was minimal around the bronchial tree, with only a smattering of inflammatory cells. In the OVA-challenged group after T. spiralis infection, the numbers of macrophages and eosinophils in the bronchial alveolar lavage fluid were reduced by 23% and 52%, respectively, as compared to those of the OVA-challenged group. Airway hyperresponsiveness of OVA-challenged mice after T. spiralis infection was significantly suppressed as compared to the OVA-only challenged mice. The T. spiralis-infected mice exhibited a significant reduction in IL-5 concentrations relative to that noted in the OVA-challenged group (p < 0.01). Nevertheless, the regulatory cytokines IL-10 and TGF-β levels were increased significantly as the result of T. spiralis infection, and we verified the recruitment of Treg cells in lung draining lymph nodes via T. spiralis infection. Therefore, Treg cells, which were recruited by T. spiralis infection, might ameliorate lung function and reduce allergic airway inflammation. 相似文献
992.
Interleukin-21 (IL-21) is a pleiotropic cytokine that regulates T-cell, B-cell, NK-cell, and myeloid-cell functions. IL-21 binds with its cognate receptor complex, which consists of the IL-21 receptor (IL-21R) and the common gamma chain. We identified a novel IL-21R-binding molecule, WSB-1, which contains WD-40 repeats and a SOCS-box domain. WSB-1 associates with the middle part of intracytoplasmic region of IL-21R and enhances the maturation of IL-21R from N-linked glycosylated form to fully glycosylated mature form. Furthermore, WSB-1 moderates IL-21R degradation. Taken together, our present study suggests that WSB-1 has a role in the tuning of the maturation and degradation of IL-21R. 相似文献
993.
Reyes JL Espinoza-Jiménez AF González MI Verdin L Terrazas LI 《Cellular immunology》2011,267(2):77-87
Helminth infections induce strong immunoregulation that can modulate subsequent pathogenic challenges. Taenia crassiceps causes a chronic infection that induces a Th2-biased response and modulates the host cellular immune response, including reduced lymphoproliferation in response to mitogens, impaired antigen presentation and the recruitment of suppressive alternatively activated macrophages (AAMФ). In this study, we aimed to evaluate the ability of T. crassiceps to reduce the severity of experimental autoimmune encephalomyelitis (EAE). Only 50% of T. crassiceps-infected mice displayed EAE symptoms, which were significantly less severe than uninfected mice. This effect was associated with both decreased MOG-specific splenocyte proliferation and IL-17 production and limited leukocyte infiltration into the spinal cord. Infection with T. crassiceps induced an anti-inflammatory cytokine microenvironment, including decreased TNF-α production and high MOG-specific production of IL-4 and IL-10. While the mRNA expression of TNF-α and iNOS was lower in the brain of T. crassiceps-infected mice with EAE, markers for AAMФ were highly expressed. Furthermore, in these mice, there was reduced entry of CD3+Foxp3− cells into the brain. The T. crassiceps-induced immune regulation decreased EAE severity by dampening T cell activation, proliferation and migration to the CNS. 相似文献
994.
995.
Hu JL Li G Zhou DX Zou YX Zhu ZS Xu RX Jiang XD Zeng YJ 《Cellular and molecular neurobiology》2009,29(1):81-85
Neuroinflammation has been implicated in the etiology of Alzheimer’s disease (AD). Many studies have suggested that C(-889)
T promoter polymorphism in one of the proinflammatory cytokine interleukin-1 (IL-1) encoding gene IL-1A may be associated
with AD pathogenesis. To determine whether the polymorphism contributes to the risk for late-onset AD (LOAD) in Chinese, we
carried out our investigation in 344 sporadic LOAD patients and 224 healthy controls. No statistical significant association
was obtained between IL-1A C(-889) T polymorphism and LOAD and no statistical difference was found between cases and controls
after stratification for apolipoprotein E allele 4 (APOE ε4) status. The results reveal that it is not likely that the IL-1A
C(-889) T polymorphism is involved in AD pathogenesis in the Chinese population. Further studies of the associations between
other IL-1A genetic polymorphisms and AD should be performed in a larger population and biologic functional analysis of IL-1A
gene is required to verify the underlying roles of IL-IA in LOAD. 相似文献
996.
Dodds MG Frederiksen KS Skak K Hansen LT Lundsgaard D Thompson JA Hughes SD 《Cancer immunology, immunotherapy : CII》2009,58(6):843-854
Purpose Recombinant interleukin-21 (rIL-21) is an immune stimulating cytokine recently tested in two Phase 1 trials for immune responsive
cancers. A secondary objective of these trials was to characterize pharmacodynamic responses to rIL-21 in patients. Here,
we report the effects of systemic rIL-21 on serum markers of immune stimulation.
Experimental design Recombinant IL-21 was administered by intravenous bolus injection at dose levels from 1 to 100 μg/kg using two distinct treatment
regimens: thrice weekly (‘3/w’) for 6 weeks; or once daily for five consecutive days followed by nine dose-free days (‘5 + 9’).
In the absence of dose limiting toxicity, additional cycles of dosing were initiated immediately following the nine dose-free
days. An array of 70 different proteins was profiled in subject serum samples from several time points during the course of
the study. Hierarchical clustering analysis was performed on a normalized subset of these data.
Results Systemic administration of rIL-21 affected the serum levels of several cytokines, chemokines, acute-phase proteins and cell
adhesion proteins. The magnitude and duration of response were dose dependent for a subset of these biomarkers. The 5 + 9
dosing regimen generally produced cyclic changes that were of greater magnitude, as compared to a more chronic stimulation
with the 3/w dosing regimen. Despite these differences, rIL-21 effects on many analytes were similar between regimens when
averaged over the time of treatment. Based on similar temporal, between-subject and dose response changes, groups of analytes
were identified that exhibited distinct components of the rIL-21-mediated immune activation. Biomarkers indicative of lymphocyte
activation (increased IL-16, decreased RANTES), acute phase response (increased CRP, ferritin), myeloid activation (increased
MDC, MIP-1 alpha), and leukocyte chemotaxis/trafficking (increased sCAMs, MCP-1) were strongly modulated in subjects treated
with rIL-21.
Conclusions Administration of rIL-21 resulted in activation of multiple cell types and immune response pathways. The changes observed
in serum proteins were consistent with coincident processes of lymphoid and myeloid cell activation and trafficking, and acute
phase response.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
997.
Ohara M Yamaguchi Y Matsuura K Murakami S Arihiro K Okada M 《Cancer immunology, immunotherapy : CII》2009,58(3):441-447
Background The FOXP3 mRNA expression and the other regulatory T cell-related molecules were investigated and compared with clinicopathological
parameters in human primary breast cancer.
Method This study included 136 breast cancer patients operated in our department from 2003 to 2006. Total RNA was extracted from
frozen normal breast and breast cancer tissues, and the expression of FOXP3, IL-10, TGFβ1 and CCL22 mRNA was evaluated using quantitative real-time RT-PCR.
Result
FOXP3, IL-10,
TGFβ1 and CCL22 mRNA expressions were significantly higher in cancer tissue than in normal tissue, not only at pT1, 2, and 3 stages but also
at the DCIS stage. There were positive correlations between FOXP3 and IL-10, FOXP3 and TGFβ1, as well as FOXP3 and CCL22 mRNA expressions, respectively. FOXP3 and IL-10 mRNA expressions were significantly upregulated in PgR-negative or HER2-positive tumors.
Conclusion These results suggest that regulatory T cells are involved in tumor onset and progression in human primary breast cancer,
possibly contributing to poor prognosis of patients with breast cancer. 相似文献
998.
Juncadella IJ Bates TC Suleiman R Monteagudo-Mera A Olson CM Navasa N Olivera ER Osborne BA Anguita J 《Biochemical and biophysical research communications》2010,402(1):105-109
Salp15 is a tick saliva protein that inhibits CD4+ T cell differentiation through its interaction with CD4. The protein inhibits early signaling events during T cell activation and IL-2 production. Because murine Experimental Autoimmune Encephalomyelitis development is mediated by central nervous system-infiltrating CD4+ T cells that are specific for myelin-associated proteins, we sought to determine whether the treatment of mice with Salp15 during EAE induction would prevent the generation of proinflammatory T cell responses and the development of the disease. Surprisingly, Salp15-treated mice developed more severe EAE than control animals. The treatment of EAE-induced mice with the tick saliva protein did not result in increased infiltration of T cells to the central nervous system, indicating that Salp15 had not affected the permeability of the blood-brain barrier. Salp15 treatment did not affect the development of antibody responses against the eliciting peptide or the presence of IFNγ in the sera. The treatment with Salp15 resulted, however, in the increased differentiation of Th17 cells in vivo, as evidenced by higher IL-17 production from PLP139-151-specific CD4+ T cells isolated from the central nervous system and the periphery. In vitro, Salp15 was able to induce the differentiation of Th17 cells in the presence of IL-6 and the absence of TGFβ These results suggest that a conductive milieu for the differentiation of Th17 cells can be achieved by restriction of the production of IL-2 during T cell differentiation, a role that may be performed by TGFβ and other immunosuppressive agents. 相似文献
999.
Macrophages play a key role in innate immune response to pathogens and in tissue homeostasis, inflammation and repair. A serpin A3G (SpiA3G) is highly induced in classically activated macrophages. We show increased localization of SpiA3G in the nucleolus and co-localization with cathepsin L, upon classical, but not alternative activation of macrophages. Despite the increased expression of cathepsin L in the nuclei of classically activated macrophages, no cathepsin activity was detected. Since only pro-inflammatory, but not anti-inflammatory stimuli induce increased nucleolar localization of SpiA3G, we propose that SpiA3g translocation into the nucleolus is important in host defense against pathogens.
Structured summary
MINT-7714245: fibrillarin (uniprotkb:P35550) and SpiA3G(uniprotkb:Q5I2A0) co-localize (MI:0403) by fluorescence microscopy(MI:0416)MINT-7714241: SpiA3G (uniprotkb:Q5I2A0) and cathepsin L(uniprotkb:P06797) co-localize (MI:0403) by fluorescence microscopy (MI:0416) 相似文献1000.
Upadhyay K Bavishi A Thakrar S Radadiya A Vala H Parekh S Bhavsar D Savant M Parmar M Adlakha P Shah A 《Bioorganic & medicinal chemistry letters》2011,21(8):2547-2549
A series of 4-styrylcoumarin have been synthesized by Knoevenagel condensation between substituted 4-methylcoumarin-3-carbonitrile and different heterocyclic or aromatic aldehydes. 4-Methylcoumarin-3-carbonitrile has been synthesized by the base catalyzed reaction between substituted 2-hydroxyacetophenone and ethyl cyanoacetate. The structures of the newly synthesized compounds were confirmed by 1H NMR, IR and mass spectral analysis. All the compounds were evaluated for their anti-inflammatory activity (against TNF-α and IL-6) and anti-tubercular activity. Compounds 6a, 6h and 6j exhibited promising activity against IL-6 with 72-87% inhibition and compound 6v showed potent activity against TNF-α with 73% inhibition at 10 μM concentration. Whereas compounds 6n, 6o, 6r and 6u showed very good anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain at <6.25 μM. 相似文献