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ABSTRACT Purpose: To describe a case of bilateral panuveitis in the setting of IgA nephropathy. Methods: Retrospective review of clinical records, fundus, and optical coherence tomographic (OCT) images, and fluorescein angiography. Results: A 36-year-old female presented with IgA nephropathy and contemporaneous ocular manifestations of one-year duration. Clinical exam demonstrated bilateral panuveitis, 3+ anterior chamber (AC) cell in the right eye (OD), and 0.5+ AC cell in the left eye (OS). Funduscopic exam demonstrated diffuse yellow drusenoid deposits bilaterally (OU), accentuated on fundus autofluorescence as focal areas of hyperautofluorescence. Deposits correlated with retinal pigment epithelium hyper-reflectivity on OCT, and choroidal hypo-fluorescence on fluorescein angiography. The patient was managed with oral prednisone. Conclusion: IgA nephropathy is a systemic autoimmune disease that may be associated with uveitis. Immunosuppression with corticosteroids appears to be an effective therapy. 相似文献
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There is limited experience in management of orthotopic heart transplant (OHT) patients with COVID-19. In this study, we present our initial experience using a standardized management algorithm. Data collection was performed on OHT patients with COVID-19 after March 10, 2020 (declaration of state of emergency in Massachusetts). Among the 358 OHT patients currently followed at our program, 5 patients (1.4%) tested positive for COVID-19 (median age 50 years [IQR, 49-58], duration post-OHT 21 years [IQR, 6-25], and 4 of 5 [80%] were men). Among the 5 OHT patients, 2 of 5 (20%) had mild disease and had no change in baseline immunosuppression therapy. Two of 5 (20%) had moderate disease and received remdesivir as part of a clinical trial and reduced immunosuppression therapy. One patient (20%) died prior to presenting to the hospital, consistent with 20% case fatality rate. Four patients (80%) are doing well 4 weeks post-discharge. In this small cohort of OHT patients with COVID-19, we report a 1.4% COVID-19 infection rate and 20% case fatality rate. All OHT patients managed under our clinical management algorithm had good short-term outcomes. Further study to estimate the true risk profile of OHT patients and validate the proposed management strategy is warranted. 相似文献
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Elayne Hondares Mark Adrian Brown Boris Musset Deri Morgan Vladimir V. Cherny Christina Taubert Mandeep K. Bhamrah David Coe Federica Marelli-Berg John G. Gribben Martin J. S. Dyer Thomas E. DeCoursey Melania Capasso 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(50):18078-18083
HVCN1 (Hydrogen voltage-gated channel 1) is the only mammalian voltage-gated proton channel. In human B lymphocytes, HVCN1 associates with the B-cell receptor (BCR) and is required for optimal BCR signaling and redox control. HVCN1 is expressed in malignant B cells that rely on BCR signaling, such as chronic lymphocytic leukemia (CLL) cells. However, little is known about its regulation in these cells. We found that HVCN1 was expressed in B cells as two protein isoforms. The shorter isoform (HVCN1S) was enriched in B cells from a cohort of 76 CLL patients. When overexpressed in a B-cell lymphoma line, HVCN1S responded more profoundly to protein kinase C-dependent phosphorylation. This more potent enhanced gating response was mediated by increased phosphorylation of the same residue responsible for enhanced gating in HVCN1L, Thr29. Furthermore, the association of HVCN1S with the BCR was weaker, which resulted in its diminished internalization upon BCR stimulation. Finally, HVCN1S conferred a proliferative and migratory advantage as well as enhanced BCR-dependent signaling. Overall, our data show for the first time, to our knowledge, the existence of a shorter isoform of HVCN1 with enhanced gating that is specifically enriched in malignant B cells. The properties of HVCN1S suggest that it may contribute to the pathogenesis of BCR-dependent B-cell malignancies.The voltage-gated proton channel HVCN1 (or HV1 or VSOP) is a small protein that conducts protons across membranes selectively (1, 2) and in a regulated manner. Previously, we described its function in B lymphocytes, where proton channels sustain B-cell receptor (BCR) signaling via regulation of reactive oxygen species production by the NADPH oxidase enzyme complex (3). In addition, we found HVCN1 to be directly associated with the BCR. Upon receptor stimulation, the BCR and HVCN1 were cointernalized to late endosomal/lysosomal organelles called “MIICs,” or MHC class II-containing compartments, where antigens bound to the BCR are digested into small peptides and loaded onto MHC class II molecules for presentation to T cells (3).HVCN1 is expressed not only by normal but also by malignant B cells, such as those in chronic lymphocytic leukemia (CLL) (3). CLL cells are characterized by their reliance on BCR signaling for survival and growth (4), so it is possible that they maintain or upregulate HVCN1 expression to sustain their growth. Other tumor cells, such as those in breast (5) and colorectal cancer (6), have been found to rely on HVCN1 for survival. In these tumor cells, proton channels prevent excessive acidification of the cytoplasm and allow increased cell migration. In malignant B cells, HVCN1 may regulate intracellular pH and at the same time sustain BCR signaling. However, its precise roles remain to be elucidated.We show here that CLL cells and other B-cell lines specifically express higher levels of a shorter isoform of HVCN1, HVCN1S. We identified the existence of two distinct isoforms of relatively similar size when immunoblotting B-cell lysates with an HVCN1-specific antibody (3). HVCN1S is only weakly expressed in normal B cells, and in light of its apparent upregulation in tumor cells, we set out to characterize its function. We show that HVCN1S responds more strongly to phosphorylation by protein kinase C (PKC) and identify the phosphorylation site. We provide evidence that HVCN1S in B cells is preferentially expressed at the plasma membrane, even upon BCR stimulation and subsequent internalization, due to a weaker association with the BCR. Finally, we show that HVCN1S expression results in stronger BCR signaling, increased proliferation, and augmented chemokine-dependent migration. Overall, our data indicate that HVCN1S is an alternative protein isoform that mediates stronger currents upon PKC phosphorylation, is more highly expressed at the plasma membrane, and can confer a growth advantage to malignant B cells. 相似文献
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Singh M Alexander K Roger VL Rihal CS Whitson HE Lerman A Jahangir A Nair KS 《Mayo Clinic proceedings. Mayo Clinic》2008,83(10):1146-1153
Frailty is characterized by vulnerability to acute stressors and is a consequence of decline in overall function and physiologic reserves. An estimated 7% of the US population older than 65 years and 30% of octogenarians are frail. The domains to define frailty include mobility, strength, balance, motor processing, cognition, nutrition, endurance, and physical activity. Pathophysiologic pathways leading to frailty involve a multisystem cascade that includes neuroendocrine dysfunction with lower insulin-like growth factor and dehydroepiandrosterone sulfate and an altered inflammatory milieu with increased levels of C-reactive protein, interleukins, tumor necrosis factor alpha, and abnormal coagulation. Frailty predicts death and heralds the transition to disability in general populations. As the population with coronary artery disease shifts toward older patients, physicians must consider the role of frailty in their patients. This review will enable clinicians to recognize frailty and consider its relevance in their daily practice. We also elaborate on reasons to consider frailty in older adults with cardiovascular disease and focus on its early identification, on referral to specialists, and on care after serious cardiac events. 相似文献
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Inferior dislocation of the hip is the rarest type in hip dislocation.Very few cases have been reported in the anglophonic literature,most of which involved the pediatric age group.Surprisingly,we came... 相似文献