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排序方式: 共有291条查询结果,搜索用时 0 毫秒
1.
The role of the carbohydrate chains in complement (C3) fixation by solid-phase-bound human IgA. 总被引:2,自引:0,他引:2
In contrast to antigen-antibody complexes containing native human IgA, solid-phase-deposited IgA activates the alternative complement pathway and binds C3b. To investigate the role of carbohydrate chains in this, various human IgA preparations were treated with neuraminidase alone or together with N-glycanase or O-glycanase, or with mixed glycosidases from the oral bacterium, Streptococcus mitis. Depletion of oligosaccharides was determined by carbohydrate analysis. Removal of sialic acid and N-linked glycan chains greatly increased the C3b-fixing properties of normal serum IgA1 and IgA2. Myeloma IgA1 and IgA2 proteins and secretory IgA had higher C3b-binding activity than normal serum IgA, and this was further increased by removal of sialic acid and N-linked glycans. Fc alpha and Fc alpha-SC fragments of myeloma and secretory IgA1, respectively, but not Fab alpha fragments, obtained by cleavage with bacterial IgA1 proteases and also free secretory component, fixed C3b by the alternative pathway. 相似文献
2.
In the present study, we examined the role of the recently identified glycosylphosphatidylinositol (GPI)-anchored cell surface molecule BY55, assigned as CD160, in TCR signaling. CD160 is expressed by most intestinal intraepithelial lymphocytes and by a minor subset of circulating lymphocytes including NK, TCRgammadelta and cytotoxic effector CD8bright+CD28- T lymphocytes. We report that CD160, which has a broad specificity for MHC class Ia and Ib molecules, behaves as a co-receptor upon T cell activation. Anti-CD160 mAb enhance the CD3-induced proliferation of freshly isolated CD160-enriched peripheral blood lymphocytes and CD160+ T cell clones. Further, the engagement of CD160 receptors on normal clonal T lymphocyte populations lacking CD4, CD8 and CD28 molecules by MHC class I molecules results in an increased CD3-induced cell proliferation. Further, we found that CD160 co-precipitates with the protein tyrosine kinase p56lck and tyrosine phosphorylated zeta chains upon TCR-CD3 cell activation. Thus, we demonstrate that CD160 provides co-stimulatory signals leading to the expansion of a minor subset of circulating lymphocytes including double-negative CD4/CD8 T lymphocytes and CD8bright+ cytotoxic effector T lymphocytes lacking CD28 expression. 相似文献
3.
Kristina Nikolova Jordan J. Steiner Judy L. Postmus Andrea Hetling Laura Johnson 《Health & social care in the community》2021,29(1):66-77
The Family Violence Option (FVO) was designed to help survivors of domestic violence (DV) more easily secure income support in the United States (U.S.), without placing them at risk of further abuse. The objective of this study is to determine whether the decision-making of advocates responsible for determining waiver recommendations under the FVO is influenced by the relationship status of DV survivors. Recursive partitioning was used to analyse data from a sample of 237 survivor risk assessments from four New Jersey counties to determine which women receive waiver recommendations and which do not. Advocates completed risk assessments for the women and were instructed to make recommendations on waivers based on their assessment. Workers’ decision-making was examined using classification and regression trees (CART) to determine what case factors made it more or less likely for survivors to be recommended waivers. The CART results were supplemented with logistic regression analyses to ensure validity. For two of three waivers, survivors who reported currently residing with their abuser or who had ended the relationship recently were less likely to receive waiver recommendations than those who had been out of the relationship for a longer period of time (OR = 0.09–0.21), even when accounting for the type and severity of DV and the impacts of the violence on survivors’ mental health. The results indicate that DV advocates’ decision-making is complicated by factors independent of survivors’ case characteristics. This can affect the safety and well-being of women attempting to leave violent relationships by affecting their access to resources. 相似文献
4.
Grant A McArthur George D Demetri Allan van Oosterom Michael C Heinrich Maria Debiec-Rychter Christopher L Corless Zariana Nikolova Sasa Dimitrijevic Jonathan A Fletcher 《Journal of clinical oncology》2005,23(4):866-873
PURPOSE: The cutaneous malignant tumor dermatofibrosarcoma protuberans (DFSP) is typically associated with a translocation between chromosomes 17 and 22 that places the platelet-derived growth factor-B (PDGFB) under the control of the collagen 1A1 promoter. The purpose of this study was to evaluate molecular, cytogenetic, and kinase activation profiles in a series of DFSPs and to determine whether these biologic parameters are correlated with the clinical responses of DFSP to imatinib. PATIENTS AND METHODS: We analyzed the objective radiologic and clinical response to imatinib at 400 mg twice daily in eight patients with locally advanced DFSP and two patients with metastatic disease. RESULTS: Each of eight patients with locally advanced DFSP had evidence of t(17;22) and showed a clinical response to imatinib. Four of these patients had complete clinical responses. The two patients with metastatic disease had fibrosarcomatous histology and karyotypes that were substantially more complex than those typically associated with localized DFSP. One patient with metastatic DFSP and an associated t(17;22) had a partial response to imatinib but experienced disease progression after 7 months of therapy. In contrast, the other patient with metastatic disease had a tumor lacking t(17;22), and there was no clinical response to imatinib. Unexpectedly, there was minimal platelet-derived growth factor receptor-beta phosphorylation in the untreated DFSP, despite the documented presence of a PDGFB autocrine mechanism. CONCLUSION: Imatinib has clinical activity against both localized and metastatic DFSP with t(17;22). However, fibrosarcomatous variants of DFSP lacking t(17;22) may not respond to imatinib. 相似文献
5.
Silvia Isabel Rech Franke Temenouga Nikolova Guecheva João Antonio Pêgas Henriques Daniel Prá 《Nutrition and cancer》2013,65(7):943-953
Orange juice (OJ) is among the most consumed fruit juices worldwide, and its chemopreventive action is fairly addressed in the literature. This review critically presents the available evidence linking OJ with cancer chemoprevention and on discussing the putative mechanisms and negative health effects. The chemopreventive action of OJ is related to its effect on metabolic enzymes and its antiinflammatory, cytoprotective/apoptotic, hormonal, cell signaling-modulating, antioxidant, and antigenotoxic effects. Most studies on OJ are in vitro, and few are conducted in vivo. Results from in vitro studies must be interpreted carefully because these findings do not consider in vivo bioavailability. However, such results are useful for studying the impact of different processing and storage methods on OJ's chemopreventive effect. Evidence of OJ's chemoprevention in humans is limited. OJ is antimutagenic in bacteria and antigenotoxic in humans and rodents. Studies using rodent cancer models showed that OJ is cancer chemopreventive, influencing either the induction stage or the promotion stage. The composition and, therefore, the chemopreventive action of OJ might be influenced by different cultivars, climates, extraction methods, packaging, storage temperatures, and shelf lives, among other factors. Epidemiological studies and randomized controlled intervention studies in humans evaluating the chemopreventive effect of OJ, taking into consideration variability in OJ composition, are needed. 相似文献
6.
Hüttner E Matthies U Nikolova T Ehrenreich H 《Alcoholism, clinical and experimental research》1999,23(2):344-348
The frequencies of structural chromosomal aberrations were analyzed in peripheral blood lymphocytes of 31 chronic alcoholics at the beginning of an intensive outpatient treatment program at a neuropsychiatric clinic and were compared with 31 controls matched for gender, age, smoking habits, and nondrinkers. A statistically significant difference was observed in the level of chromosomal aberrations in somatic cells from alcoholics when compared with controls (3.01% vs. 1.28%, p < or = 0.001). A follow-up study was carried out for a subset of the patients after 3 months (8 subjects) and 12 months (14 subjects) of controlled abstinence. A statistically significant increase in the mean frequency of cells with aberrations was observed in the group of 14 subjects reinvestigated after 12 months of abstinence when compared with the mean value of the first blood samples immediately after hospitalization (4.61% vs. 3.01%; p < or = 0.001). An excessive increase in cigarette consumption during alcohol abstinence, reflected by a dramatic elevation of CO-hemoglobin levels, may, at least in part, account for this finding. In conclusion, chronic alcoholism leads to genotoxic effects that, instead of recovering after 1 year of alcohol abstinence, are even enhanced, most likely due to the "shift in addictive behavior." 相似文献
7.
8.
The increasing data provides enough evidences confirming the involvement of free radicals and other reactive oxygen species (ROS) superoxide radical ( . O 2 ? ), nitric oxide (NO . ), hydrogen peroxide (H2O2) and hydroxyl radicals ( . OH) in a number of physiological and pathological processes. Imbalance between levels of ROS resulting in the body and the capacity of antioxidant defense mechanisms occur oxidative stress (OS). OS is related to a number of structural and functional damages to cells and is involved in the pathogenesis of many diseases, including neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease (PD), amyotrophic lateral sclerosis, and Huntington disease. Defects in oxidative phosphorylation and oxidative damage play an important role in neurodegenerative diseases. The aim of this study was to investigate some biomarkers of OS such as the level of lipid peroxidation measured as malondialdehyde (MDA) reactive products and activity of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in the blood of PD patients compared with control group of healthy volunteers. By the present research we report higher levels of MDA products and an imbalance in SOD and CAT enzyme activities in PD patients compared to the control group. 相似文献
9.
Semirational design of active tumor suppressor p53 DNA binding domain with enhanced stability 总被引:8,自引:1,他引:8 下载免费PDF全文
Penka V. Nikolova Julia Henckel David P. Lane Alan R. Fersht 《Proceedings of the National Academy of Sciences of the United States of America》1998,95(25):14675-14680
We have designed a p53 DNA binding domain that has virtually the same binding affinity for the gadd45 promoter as does wild-type protein but is considerably more stable. The design strategy was based on molecular evolution of the protein domain. Naturally occurring amino acid substitutions were identified by comparing the sequences of p53 homologues from 23 species, introducing them into wild-type human p53, and measuring the changes in stability. The most stable substitutions were combined in a multiple mutant. The advantage of this strategy is that, by substituting with naturally occurring residues, the function is likely to be unimpaired. All point mutants bind the consensus DNA sequence. The changes in stability ranged from +1.27 (less stable Q165K) to −1.49 (more stable N239Y) kcal mol−1, respectively. The changes in free energy of unfolding on mutation are additive. Of interest, the two most stable mutants (N239Y and N268D) have been known to act as suppressors and restored the activity of two of the most common tumorigenic mutants. Of the 20 single mutants, 10 are cancer-associated, though their frequency of occurrence is extremely low: A129D, Q165K, Q167E, and D148E are less stable and M133L, V203A and N239Y are more stable whereas the rest are neutral. The quadruple mutant (M133LV203AN239YN268D), which is stabilized by 2.65 kcal mol−1 and Tm raised by 5.6°C is of potential interest for trials in vivo. 相似文献
10.
Maria Nikolova Svetoslav Magaev Zachariy Krastev 《Scandinavian journal of gastroenterology》2013,48(9):1145-1146
During intravenous treatment with terlipressin for recurrent gastrointestinal (GI) bleeding, a 50-year-old male with no history of heart disease developed a newly prolonged QT interval and torsade de pointes. Risk factors present for acquired long QT syndrome were mineral dysbalance and a history of alcohol abuse with hepatic impairment. The patient was brought back to a normal sinus rhythm after a single 300-J counter-shock. Terlipressin was discontinued, and the patient's QTc interval subsequently returned to baseline. During 6 weeks of monitoring, arrhythmia did not recur. 相似文献