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411.
Devauchelle-Pensec V Pennec Y Morvan J Pers JO Daridon C Jousse-Joulin S Roudaut A Jamin C Renaudineau Y Roué IQ Cochener B Youinou P Saraux A 《Arthritis and rheumatism》2007,57(2):310-317
OBJECTIVE: There is evidence to support a dominant role for B cells in the pathophysiology of primary Sj?gren's syndrome (SS). Therefore, we evaluated the safety and efficacy of anti-CD20 monoclonal antibody. METHODS: Sixteen patients who met the new American-European Consensus Group criteria for primary SS and scored >50 on at least 2 of 4 visual analog scales (VAS; 100 mm) evaluating global disease, pain, fatigue, and global dryness received infusions of low-dose rituximab (375 mg/m(2)) at weeks 0 and 1 without steroid premedication. RESULTS: Slow rituximab infusions (100 mg/hour) were well tolerated, with only 1 patient experiencing serum sickness-like disease. There was a dramatic reduction in B cells of the blood and salivary gland (SG). At week 12, VAS scores with respect to fatigue and dryness (P < 0.05), tender point count (P < 0.035), and quality of life as evaluated by the Short Form 36 questionnaire (SF-36; P < 0.001) were significantly improved. At week 36, significant improvements were noted in the 4 VAS scores (P < 0.05), tender joint count (P = 0.017), tender point count (P = 0.027), and SF-36 (P < 0.03). Pulmonary manifestations were ameliorated in 1 patient. Patients with improvements on at least 3 of the 4 VAS scores at any visit (n = 11) had a shorter disease duration than the other patients (n = 5; mean +/- SD duration 3.8 +/- 5.4 versus 30.1 +/- 29.5 years; P = 0.02). CONCLUSION: Low-dose rituximab infusions were well tolerated without the benefit of steroids. Infusions induced a rapid depletion of B cells in the blood and SG and could improve primary SS. Controlled studies are needed. 相似文献
412.
BAFF-modulated repopulation of B lymphocytes in the blood and salivary glands of rituximab-treated patients with Sjögren's syndrome 总被引:2,自引:0,他引:2
Pers JO Devauchelle V Daridon C Bendaoud B Le Berre R Bordron A Hutin P Renaudineau Y Dueymes M Loisel S Berthou C Saraux A Youinou P 《Arthritis and rheumatism》2007,56(5):1464-1477
OBJECTIVE: Treatment with rituximab depletes B cells from the peripheral blood (PB) and salivary glands (SGs) of patients with primary Sj?gren's syndrome (SS). The purpose of this study was to track the repopulation of B cell subsets in PB as well as their subsequent homing into SGs in patients with primary SS treated with rituximab. METHODS: A series of 4-color flow cytometry experiments delineated B cell subsets in 15 patients with primary SS. All were tested on days 8 and 15 of treatment. Nine of the patients were followed up monthly for 10 months, and the remaining 6 patients were followed up monthly for 24 months. Enzyme-linked immunosorbent assays were developed to measure serum levels of BAFF and rituximab. SGs were biopsied at the start of the study and 4 months after treatment in 15 patients, 12 months after treatment in 3 patients, and 24 months after treatment in 2 patients. RESULTS: Baseline serum levels of BAFF correlated inversely (r = -0.92, P < 5 x 10(-4)) with the duration of B cell depletion: the higher the BAFF levels, the shorter the duration of B cell depletion. Four B cell subsets repopulated the PB: plasmablasts (CD19+, CD5-,IgD-,CD38++), transitional type 1 (T1) B cells (CD19+,CD5+,IgD+,CD38++), mature Bm2 cells (CD19+,CD5+/-,IgD+,CD38+/-), and memory B cells (CD19+,CD5-,IgD-,CD38-). Increased numbers of Bm2 cells and decreased memory B cells reappeared with time. Sequential SG biopsies revealed that B cells were absent in these glands for 12 months: they were detected 24 months after rituximab treatment. Memory and T1 B cells were the first B cells identified locally. CONCLUSION: The timing of B cell repopulation is modulated by BAFF and is followed by reconstitution of the preexisting abnormalities. 相似文献
413.
B lymphocytes on the front line of autoimmunity 总被引:4,自引:0,他引:4
The paradigm that B cell response to self antigens (Ag) is promoted by antibodies (Ab) has become unsatisfactory. Studies over the last decade have indeed revealed that B cells serve extraordinarily diverse functions within the immune system other than Ab production. They normally play a role in the development in the regulation, as well as the activation of lymphoid architecture, regulating dentritic cells and T cell subsets function through cytokine production. Receptor editing is also essential in B cells and aids in preventing autoimmunity. Both abnormalities in the distribution of B cells subsets and clinical benefit response to B cell depletion in autoimmune states illustrate their importance. Transgenic animal models have demonstrated that sensitivity of B cells to Ag receptor cross-linking correlates to autoimmunity: negative signaling by CD5 and CD22 in maintaining tolerance through recruitment of phosphatase has thus been documented. In short, a new area has been reached, whereby B lymphocytes return as a significant contributor to autoimmune disorders. 相似文献
414.
Le Dantec C Varin MM Brooks WH Pers JO Youinou P Renaudineau Y 《Current pharmaceutical biotechnology》2012,13(10):2046-2053
There is growing evidence that epigenetics, the study of heritable changes in gene expression that do not involve mutations in the DNA itself, may play an essential role in autoimmune diseases (AID). In Sj?gren's syndrome (SS), a chronic AID characterized by an epithelis of the exocrine glands, epigenetic studies have focused on three mechanisms: DNA methylation and its consequences including human endogenous retrovirus (HERV) expression; microRNA expression; and protein post-translational modifications associated with autoantibody production. Although in its infancy, comprehension of the epigenetic (dys)regulation in SS may help us to understand: why SS affects predominantly middle-aged women; why genetically predisposed individuals develop SS but not others; why flare-ups occur; why treatment responses differ between patients; and why some patients develop lymphoma. From these studies will arise a better comprehension of the pathophysiology of SS as well as development of new diagnostic and prognostic biomarkers, and novel therapeutics for prevention and perhaps early intervention. 相似文献
415.
Séité JF Guerrier T Cornec D Jamin C Youinou P Hillion S 《Journal of autoimmunity》2011,37(3):190-197
One way for intravenous Ig (IVIg) to affect responses of the B cells might be to operate through their TLR7 and TLR9. We confirm the ability of TLR agonists to induce CD25 expression in B cells. For this to occur, sialylated Fc-gamma of IgG included in the IVIg preparation are required. As a result, IVIg suppresses TLR-induced production of the proinflammatory IL-6, but not that of the anti-inflammatory IL-10. That is, IVIg mimics the effects of the MyD88 inhibitor. Finally, as we previously showed that IVIg induces CD22 to recruit the inhibitory SHP-1, we established that this enzyme was also involved in IVIg-induced inhibition of TLR9 signaling. This is the first report to demonstrate such a mechanism underlying the negative impact of IVIg on B lymphocytes. 相似文献
416.
Following allogenic hematopoietic stem cell transplantation (HSCT), patients with autoimmune disease or hematopoietic malignancy may develop acute or chronic graft-versus-host (GvH) disease. B lymphocytes, from the recipient as well as from the donor, have recently been implicated in the pathogenesis of such disturbances. Their deleterious effects are accounted for by other tasks B lymphocytes accomplish than the antibody production. We highlight herein some recent observations in the context of B cells in the GvH disease. 相似文献
417.
418.
川藏香茶菜中双聚对映贝壳杉烯的结构鉴定 总被引:1,自引:0,他引:1
从川藏香茶菜的干叶和嫩枝中,分离得到了一个对映贝壳杉烯的双聚体,命名为川藏香茶菜戊素,经光谱解析和化学证明确定了其结构为川藏香茶菜甲素的Diels-Alder双聚体。 相似文献
419.
420.
Yves Renaudineau Sabine Croquefer Sandrine Jousse Eric Renaudineau Valrie Devauchelle Paul Guguen Catherine Hanrotel Boris Gilburd Alain Saraux Yehuda Shoenfeld Chaim Putterman Pierre Youinou 《Arthritis \u0026amp; Rheumatology》2006,54(8):2523-2532