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1.
Waldenström macroglobulinemia (WM) is a rare subtype of non-Hodgkin lymphoma characterized by malignant lymphoplasmacytic cells in the bone marrow (BM). To dissect the pathophysiology of WM, we evaluated clonal cells by mapping of B cell lymphomagenesis with adaptive and innate immune tumor microenvironment (TME) in the BM of WM patients using mass cytometry (CyTOF). In-depth immunophenotypic profiling of WM cells exhibited profound expansion of clonal cells in both unswitched and switched memory B cells and also plasma cells with aberrant expression variations. WM B lymphomagenesis was associated with reduction of most B cell precursors assessed with the same clonally restricted light chain and phenotypic changes. The immune TME was infiltrated by mature monocytes, neutrophils and adaptive T cells, preferentially subsets of effector T helper, effector CTL and effector memory CTL cells that were associated with superior overall survival (OS), in contrast to progenitors of T cells and myeloid/monocytic lineage subsets that were suppressed in WM cohort. Moreover, decrease in immature B and NKT cells was related to worse OS in WM patients. Innate and adaptive immune subsets of WM TME were modulated by immune checkpoints, including PD-1/PD-L1&PD-L2, TIGIT/PVR, CD137/CD137-L, CTLA-4, BTLA and KIR expression. The response of ibrutinib treatment to the reduction of clonal memory B cell was associated with high levels of immature B cells and effector memory CTL cells. Our study demonstrates that CyTOF technology is a powerful approach for characterizing the pathophysiology of WM at various stages, predicting patient risk and monitoring the effectiveness of treatment strategies.  相似文献   
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Purpose: to identify postural balance changes in subjects with low back pain after the application of Kinesio Taping, which is then compared to a no treatment control group, using baropodometric evaluation. Methods: This randomized controlled trial was carried out on 50 individuals (both sexes) with chronic low back pain. They were then randomized into two groups: an experimental group - EG (treated with Kinesio Taping in the lumbar region) and a control group - CG (no intervention). Both groups underwent a baropodometric evaluation (mean plantar pressure, peak plantar pressure, plantar surface, mass distribution on right foot and left foot, mass distribution on forefoot and rear foot and base width) at four different moments: pre-intervention, 10 minutes, 48 hours, and 10 days after the intervention on the EG. The level of statistical significance was established at 5%. Results: Significant changes were observed in the EG compared to the CG. In the EG, peak pressure reduced on both right and left foot after Kinesio Taping application; the right base width was reduced, and the mass distribution between the forefoot and the rear foot normalized towards the ideal 50% distribution. These changes happened 48 hours after the Kinesio Taping application, with effects lasting up to 10 days. Conclusion: The use of Kinesio Taping in the lumbar region of subjects with chronic low back pain improved postural balance. This is proved by changes in peak plantar pressure, plantar surface, and mass distribution 48 h after Kinesio Taping application, with effects lasting up to 10 days.  相似文献   
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Objective

To translate and cross-culturally adapt the Pelvic Girdle Questionnaire (PGQ) into Brazilian Portuguese and test the measurement properties of the PGQ and the Roland Morris Disability Questionnaire (RMDQ) in women with pelvic pain during pregnancy.

Methods

Thirty pregnant women were included in the assessment of the pre-test of the final version of the PGQ and 100 were included in the assessment of the measurement properties. In the initial assessment, the PGQ, RMDQ, pain numerical rating scale, and WHOQOL-BREF were applied to test the internal consistency and construct validity. In the 48-hour assessment, only the PGQ and RMDQ were applied to test reliability and measurement error; in the reassessment after one month, the PGQ, RMDQ, and global perceived effect scale were applied to evaluate responsiveness.

Results

The PGQ showed adequate internal consistency (Cronbach's alpha = 0.83), substantial reliability (ICC2,1 = 0.85), very good measurement error (5%), and good responsiveness (r = ?0.62). We also observed good correlation with disability and quality of life in the physical health domain, moderate correlation with pain and quality of life in the psychological domain, and poor correlation with quality of life in the domains social relationships and environment. The RMDQ showed adequate internal consistency (Cronbach's alpha = 0.80), substantial reliability (ICC2,1 = 0.76), good measurement error (9%), moderate responsiveness (r = ?0.51), moderate correlation with quality of life in the physical health and psychological domains, and weak correlation with pain and quality of life in the social relationships and environment domains.

Conclusion

The Brazilian Portuguese version of the PGQ showed superior measurement properties compared to the RMDQ, being a valid, reliable, and responsive instrument for assessing patients with pelvic pain during pregnancy.  相似文献   
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Enhancing skin allograft longevity lessens the need for new allografts before optimal intervention is available. Reduced activity of ADAMTS13 (an enzyme that cleaves the pro‐thrombotic and proinflammatory von Willebrand factor) and presence of neutrophil extracellular traps (NETs) have been implicated in liver and lung allograft failures. The effect of ADAMTS13 treatment and the impact of NETs on skin allografts, however, remain unexplored. Here, we adopted a murine model of complete mismatch full‐thickness skin transplant by grafting dorsal skin from BALB/c mice to C57BL/6J background mice. Recombinant human ADAMTS13 (rhADAMTS13) treatment of graft recipients increased allograft survival. Western blot and immunofluorescence microscopy revealed the presence of NETs in allografts of vehicle, but surprisingly, not in rhADAMTS13‐treated mice, 3 days after surgery. Recapitulating the observations in mice, NETs were also observed in all the examined allografts from burn patients. Intriguingly, knocking out peptidylarginine deiminase 4 (PAD4, a key enzyme for NET formation) or DNase 1 treatment (which cleaves NETs) also prolonged allograft survival. In summary, rhADAMTS13 lessens inflammation in allografts by reducing NET burden, resulting in enhanced allograft survival. RhADAMTS13 and anti‐NET treatments could be new therapeutic strategies to promote skin allograft longevity and, hence, the survival of patients with severe burns.  相似文献   
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Background

Proton-pump inhibitors (PPIs) are often prescribed to patients receiving dual antiplatelet therapy (DAPT). However, this class of medication, especially omeprazole, has been associated with a reduction in clopidogrel efficacy, leading many clinicians to substitute omeprazole with ranitidine.

Objectives

Our objective was to compare the antiplatelet effect of clopidogrel before and after the addition of omeprazole or ranitidine.

Methods

We measured platelet aggregability at baseline and after 1 week of clopidogrel 75 mg daily. Subjects were then randomized in a double-blinded, double-dummy fashion to omeprazole 20 mg twice daily (bid) or ranitidine 150 mg bid. We repeated aggregability tests after 1 additional week, using VerifyNow P2Y12? (Accumetrics; San Diego, CA, USA), depicting aggregability as percent inhibition of platelet aggregation (IPA).

Results

We enrolled 41 patients in the omeprazole group and 44 in the ranitidine group. IPA was significantly decreased after the addition of omeprazole to clopidogrel (from 26.3 ± 32.9 to 17.4 ± 33.1 %; p = 0.025), with no statistical significant changes observed in the ranitidine group (from 32.6 ± 28.9 to 30.1 ± 31.3 %; p = 0.310). The comparison of IPA in both groups at the end of the follow-up showed a trend toward significance (p = 0.07, 95 % confidence interval [CI] ?1.19 to 26.59); after excluding homozygous patients for 2C19*2 genotype, the comparison of IPA between the groups reached statistical significance (32.7 ± 30.8 vs. 17.7 ± 33.4 %, respectively, for ranitidine and omeprazole groups; p = 0.04).

Conclusions

Unlike omeprazole, ranitidine did not influence platelet aggregability response to clopidogrel.

Clinical Trial Registration

NCT01896557.
  相似文献   
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