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171.
Yong Zhou Jie Zha Zhijuan Lin Zhihong Fang Hanyan Zeng Jintao Zhao Yiming Luo Zhifeng Li Bing Xu 《Experimental cell research》2018,362(2):287-292
Diffuse large B cell lymphoma (DLBCL) is a common B cell malignancy with approximately 30% of patients present relapsed or refractory disease after first-line therapy. Research of further treatment options is needed. Cytotoxic CD4+ T cells express cytolytic molecules and have potential antitumor function. Here, we showed that the CD19+ cells from DLBCL patients presented significantly reduced expression of MHC II molecules than those from healthy controls. Three years after the first-line treatment, patients that presented relapsed disease had significantly lower MHC II expression on their CD19+ cells than patients who did not show recurrence. Examining cytotoxic CD4+ T cells show that DLBCL patients presented significantly elevated frequencies of granzyme A-, granzyme B-, and/or perforin-expressing cytotoxic CD4+ T cells. Also, frequency of cytotoxic CD4+ T cells in DLBCL patients was positively correlated with the MHC II expression level. Subsequently, the cytotoxic potential of CD4+ T cells against autologous CD19+ cells was investigated. We found that the cytotoxic potential of CD4+ T cells was highest in MHC II-high, intermediate in MHC II-mid, and lowest in MHC II-low patients. The percentage of MHC II-expressing viable CD19+ cells presented a significant reduction after longer incubation with cytotoxic CD4+ T cells, suggesting that cytotoxic CD4+ T cells preferentially eliminated MHC II-expressing CD19+ cells. Blocking MHC II on CD19+ cells significantly reduced the cytolytic capacity of CD4+ T cells. Despite these discoveries, the frequency of cytotoxic CD4+ T cells did not predict the clinical outcome of DLBCL patients. Together, these results demonstrated that cytotoxic CD4+ T cells presented an MHC II-dependent cytotoxic potential against autologous CD19+ cells and could potentially represent a future treatment option for DLBCL. 相似文献
172.
Selenium unmasks protective iron armor: A possible defense against cutaneous inflammation and cancer
Jack L. Arbiser Michael Y. Bonner Nicole Ward Justin Elsey Shikha Rao 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(11):2518-2527
Background
A link between selenium deficiency and inflammatory skin diseases have been noted by many, but this link is still not well understood. We have previously studied the efficacy of ceramide analogs, based on the fire ant venom Solenopsin A, against our psoriasis animal model. Treatment of animals with solenopsin analogs resulted in significantly improved skin as well as in a coordinate downregulation of selenoproteins, namely Glutathione Peroxidase 4 (GPX4). We thus hypothesize that ferroptosis may be a physiologic process that may protect the skin from both inflammatory and neoplastic processes.Methods
We analyze and compare gene expression profiles in the GEO database from clinical skin samples taken from healthy patients and psoriasis patients (both involved and noninvolved skin lesions). We validated the gene expression results against a second, independent, cohort from the GEO database.Results
Significant reduction in gene expression of GPX4, elevated expression of Nrf2 downstream targets, and expression profiles mirroring erastin-inhibition of Cystine/Glutamate Antiporter-System XC activity in psoriatic skin lesions, compared to both noninvolved skin and healthy patient samples, suggest an innately inducible mechanism of ferroptosis.Conclusions
We present data that may indicate selenoproteins, particularly GPX4, in resolving inflammation and skin cancer, including the novel hypothesis that the human organism may downregulate GPX4 and reactive oxygen (REDOX) regulating proteins in the skin as a way of resolving psoriasis and nonmelanoma skin cancer through increased reactive oxygen species. Further studies are needed to investigate ferroptosis as a possible physiologic mechanism for eliminating inflammatory and malignant tissues.General significance
This study provides a fresh framework for understanding the seemingly contradictory effects of selenium supplementation. In addition, it offers a novel explanation of how physiologic upregulation of ferroptosis and downregulation of selenoprotein synthesis may mediate resolution of inflammation and carcinogenesis. This is of therapeutic significance. 相似文献173.
Fatal primary diffuse large B‐cell lymphoma of the maxillary sinus initially treated as an infectious disease in an elderly patient: A clinicopathologic report 下载免费PDF全文
Mayara Santos de Castro Cínthia Magalhães Ribeiro Marina Lara de Carli Alessandro Antônio Costa Pereira Felipe Fornias Sperandio Oslei Paes de Almeida João Adolfo Costa Hanemann 《Gerodontology》2018,35(1):59-62
Objective
To report a case of primary diffuse large B‐cell lymphoma (DLBCL) of the maxillary sinus in an 82‐year‐old Caucasian woman.Background
Diffuse large B‐cell lymphoma of the maxillary sinus has non‐specific signs and symptoms that may be confused with benign inflammatory conditions and upper respiratory infections.Methods
An incisional biopsy was performed. CD20+/CD3–/Ki‐67: 95% cells were observed.Conclusion
A good medical history, clinical and imaging evaluations and immunohistochemical reactions are crucial to establish a correct and early diagnosis of DLBCL. 相似文献174.
N-aryl-piperidine-4-carboxamides as a novel class of potent inhibitors of MALT1 proteolytic activity
Achim Schlapbach Laszlo Revesz Carole Pissot Soldermann Thomas Zoller Catherine H. Régnier Frédéric Bornancin Thomas Radimerski Jutta Blank Ansgar Schuffenhauer Martin Renatus Paulus Erbel Samu Melkko Richard Heng Oliver Simic Ralf Endres Markus Wartmann Jean Quancard 《Bioorganic & medicinal chemistry letters》2018,28(12):2153-2158
Starting from a weak screening hit, potent and selective inhibitors of the MALT1 protease function were elaborated. Advanced compounds displayed high potency in biochemical and cellular assays. Compounds showed activity in a mechanistic Jurkat T cell activation assay as well as in the B-cell lymphoma line OCI-Ly3, which suggests potential use of MALT1 inhibitors in the treatment of autoimmune diseases as well as B-cell lymphomas with a dysregulated NF-κB pathway. Initially, rat pharmacokinetic properties of this compound series were dominated by very high clearance which could be linked to amide cleavage. Using a rat hepatocyte assay a good in vitro-in vivo correlation could be established which led to the identification of compounds with improved PK properties. 相似文献
175.
Antonio Villalobo Hiroaki Ishida Hans J. Vogel Martin W. Berchtold 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2018,1865(3):507-521
Calmodulin (CaM) is a universal regulator for a huge number of proteins in all eukaryotic cells. Best known is its function as a calcium-dependent modulator of the activity of enzymes, such as protein kinases and phosphatases, as well as other signaling proteins including membrane receptors, channels and structural proteins. However, less well known is the fact that CaM can also function as a Ca2 +-dependent adaptor protein, either by bridging between different domains of the same protein or by linking two identical or different target proteins together. These activities are possible due to the fact that CaM contains two independently-folded Ca2 + binding lobes that are able to interact differentially and to some degree separately with targets proteins. In addition, CaM can interact with and regulates several proteins that function exclusively as adaptors. This review provides an overview over our present knowledge concerning the structural and functional aspects of the role of CaM as an adaptor protein and as a regulator of known adaptor/scaffold proteins. 相似文献
176.
IRE1α (Inositol Requiring kinase Enzyme 1 alpha), a transmembrane protein localized to the endoplasmic reticulum (ER) is a master regulator of the unfolded protein response (UPR) pathway. The fate determining steps during ER stress-induced apoptosis are greatly attributed to IRE1α’s endoribonuclease and kinase activities. Apart from its role as a chief executioner in ER stress, recent studies have shown that upon activation in the presence or absence of ER stress, IRE1α executes multiple cellular processes such as differentiation, immune response, progression and repression of the cell cycle. Besides its crucial role in protein misfolding, the versatile contributions of IRE1α in other cellular functions are greatly unknown. In this review, we have discussed the structural conservation of IRE1 among eukaryotes, the mechanisms underlying its activation and the recent understandings of the non-apoptotic functions of IRE1 other than ER stress-induced cell death. 相似文献
177.
Dilip Bhattacharjee 《Mutation research》1996,358(2):1113-235
Thymic lymphoma (TL) was observed in different stages of development in 46% of male mice (23/50) following exposure to an acute challenge dose of 2 Gy 60Co γ-rays. With an adapting dose of 1 cGy 24 h prior to the challenge dose of 2 Gy, similar growth of TL was seen in 42.5% of mice (17/40). TL was not found in unirradiated control mice (0/50) or in the group treated with 1 cGy (0/50). Multiple adapting doses for 5 or 10 consecutive days induced TL in 8/50 and 9/50 mice, respectively (17% in average). When multiple adapting doses were followed by the challenge dose, the yield of TL was much lower, 16% (8/50) and 30% (15/30), respectively. By 15, 30, 60, 90, and 120 days after exposure with 3 Gy of 60Co γ-rays, TL developed in 30, 70, 70, 80 and 85% of the female mice, respectively. When mice were conditioned with an adapting dose of 1 cGy 24 h prior to the challenge dose, TL was not found 15 days post-irradiation, while about a 25% reduction in the occurrence of TL was noticed at all other intervals. The results suggested that an adapting dose could play a role in bringing about a change in terms of delay and inhibition of the acute effects of radiation, i.e., the onset of TL in mice. 相似文献
178.
Jerry M. Gonzales 《Journal of neurochemistry》1995,64(6):2559-2566
Abstract: Cyclic AMP (cAMP) regulates many important physiological processes. Barbiturates influence cAMP regulation, possibly through effects on G proteins. This study used intact S49 mouse lymphoma cells to characterize the role of G proteins in the effect of barbiturates on cAMP regulation. cAMP accumulation was determined in intact S49 WT (wild-type) and S49 cyc? cells (the Gsα-deficient mutant) by measuring the conversion of [3H]-ATP to [3H]cAMP in cells preloaded with [3H]adenine. Pentobarbital enhanced cAMP accumulation in WT cells in the absence (basal) or presence of isoproterenol but had no effect on the EC50 for isoproterenol. This effect was dose dependent with a 50–60% enhancement at 2 mM pentobarbital. Pentobarbital did not affect forskolin-stimulated cAMP accumulation in WT cells. In cyc? cells, basal and forskolin-stimulated cAMP accumulation were stimulated only at the highest concentration of pentobarbital used (2 mM). Pentobarbital did not affect the inhibition of cAMP accumulation by somatostatin in WT cells, and pertussis toxin treatment of WT cells did not affect the action of pentobarbital on cAMP accumulation. Pentobarbital did not affect isoproterenol-stimulated adenylyl cyclase activity in whole-cell homogenates or membranes prepared from WT cells. The S-(?)-isomer of pentobarbital enhanced isoproterenol-stimulated cAMP accumulation more than the R-(+)-isomer. Phenobarbital and barbituric acid did not enhance isoproterenol-stimulated cAMP accumulation, whereas the anesthetic barbiturates hexobarbital, pentobarbital, and thiopental all enhanced activity. These results suggest that pentobarbital enhances cAMP accumulation in intact WT cells by a mechanism that is dependent on Gsα but independent of Gi. The properties of barbiturates that are responsible for the enhancement of cAMP accumulation may be related to the properties that are responsible for producing sedation and anesthesia. 相似文献
179.
Gijsbert C. de Gast Inez-Anne Haagen Anja A. van Houten Sigrid C. Klein Ashley J. Duits Roel A. de Weger Thea M. Vroom Mike R. Clark Jenny Phillips Anette J. G. van Dijk Wim B. M. de Lau Bert J. E. G. Bast 《Cancer immunology, immunotherapy : CII》1995,40(6):390-396
A bispecific antibody directed to T and B cells (CD3×CD19 bsAb) was daily infused intravenously in escalating doses from 10 g up to 5 mg in three patients with chemotherapy-resistant non-Hodgkin lymphoma; in this way we aimed to activate T cells to kill the malignant B cells. Only limited toxicity was observed, consisting of moderate fever preceded by chills or shivers and mild thrombocytopenia. No human anti-(mouse Ig) antibodies were found. Pharmacokinetics showed at
1/2 of 10.5 h with peak levels of 200–300 ng/ml after infusion of 2.5 mg bsAb. bsAb in serum was functionally active in vitro. After bsAb infusion a rise in serum tumour necrosis factor was observed, accompanied by an increase in soluble CD8 and to some extent in soluble interleukin-2 receptor (IL-2R), but not in interferon , IL-4 or soluble CD4. No evidence was found for monocyte activation (no increases in IL-6, IL-8 or IL-1ß in serum). No gross changess in histology or number of IL-2R+, CD4+ or CD8+ cells were found in the lymph nodes after therapy, but one patient showed activated CD8+ T cells within the tumour nodules. In conclusion, after intravenously administered CD3×CD19 bsAb only moderate toxicity was found, probably due to CD8+ T cell activation and cytokine release, without CD4+ T cell activation. 相似文献
180.
Daisei Miyamoto Takao Ueno Sachiko Takashima Kazuhide Ohta Toshio Miyawaki Takashi Suzuki Yasuo Suzuki 《Glycoconjugate journal》1997,14(3):379-388
A new monoclonal antibody (TU-1) directed against the Galα1-4Galβ1-4Glc residue of the Gb3Cer/CD77 antigen was prepared by
the hybridoma technique following immunization of mice with an emulsion composed of monophosphoryl lipid A, trehalose dimycolate,
and Gb3Cer isolated from porcine erythrocytes. TU-1 showed reactivity towards Gb3Cer and lyso-Gb3Cer (Galα1-4Galβ1-4Glcβ1-1′Sph),
although the reactivity towards lyso-Gb3Cer was about 10-fold lower than that to Gb3Cer. But it did not react with other structurally-related
glycolipids, such as LacCer (Galβ1-4Glcβ1-1′Cer), Gg3Cer, Gg4Cer, Gb4Cer (GalNAcβ1-3Galα1-4Galβ1-4Glcβ1-1′Cer), galactosylparagloboside
(Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glcβ1-1′Cer), sulfatide (HSO3-3Galβ1-1′Cer), other gangliosides (GM3, GM2, GM1a, GD1a and
GT1b), or P1 antigen (Galα1-4Galβ1-4GlcNAcβ1-3Galβ1-4Glcβ1-1′Cer) among neutral glycolipids prepared from P1 phenotype red
blood cells. Furthermore, TU-1 reacted with viable lymphoma cells, such as human Burkitt lymphoma cell line, Daudi, and Epstein-Barr
virus (EBV)-transformed B cells by the immunofluorescence method, and also with germinal centre B cells in human tonsil and
vessel endothelial cells in human thymus histochemically. These results indicate that TU-1 is a monoclonal antibody directed
against Gb3Cer/CD77 antigen and can be utilized as a diagnostic reagent for Burkitt's lymphoma and also for detection of the
blood group Pk antigen in glycolipid extracts of erythrocytes. Abbreviations: ATL, adult T-cell leukaemia; BSA, bovine serum
albumin; Cer, ceramide; DPPC, L-α-dipalmitoylphosphatidylcholine; EBV, Epstein-Barr virus; FCS, fetal calf serum; GalCer,
Galβ1-1′Cer; GlcCer, Glcβ1-1′Cer; LacCer, Galβ1-4Glcβ1-1′Cer; Gb3Cer, Galα1-4Galβ1-4Glcβ1-1′Cer; Iyso-Gb3Cer, Galα1-4Galβ1-4Glc1-1′Sph;
Gb4Cer, GalNAcβ1-3Galα1-4Galβ1-4Glc1-1′Cer; galactosylparagloboside, Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glcβ1-1′Cer; Gg3Cer, GalNAcβ1-4Galβ1-4Glcβ1-1′Cer;
Gg4Cer, Galβ1-3GalNAcβ1-4Galβ1-4Glcβ1-1′Cer; GM3, Neu5Acα2-3Galβ1-4Glcβ1-1′Cer; GM2, GalNAcβ1-4(Neu5Acα2-3) Galβ1-4Glcβ1-1′Cer;
GM1a, Galβ1-3GalNAcβ1-4(Neu5Acα2-3)Galβ1-4Glcβ1-1′Cer; GD1a, Neu5Acα2-3Galβ1-3GalNAcβ1-4(Neu5Acα2-3)Galβ1-4Glcβ1-1′Cer; GD1b,
Galβ1-3GalNAcβ1-4(Neu5Acα2-8Neu5Acα2-3)Galβ1-4Glcβ1-1′Cer; GT1b, Neu5Acα2-3Galβ1-3GalNAcβ1-4(Neu5Acα2-8Neu5Acα2-3) Galβ1-4Glcβ1-1′Cer;
HRP, horseradish peroxidase; LDH, lactate dehydrogenase; MAb, monoclonal antibody; MPL, monophosphoryl lipid A; P1 antigen,
Galα1-4Galβ1-4GlcNAcβ1-3Galβ1-4Glcβ1-1′Cer; PVP, polyvinylpyrolidone; Sph, sphingosine; sulfatide, HSO3-Galβ1-1′Cer; TDM,
trehalose dimycolate; TLC, thin-layer chromatography
This revised version was published online in November 2006 with corrections to the Cover Date. 相似文献