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Béla Nagy Zsolt Bene Zsolt Fejes Sonya L. Heltshe David Reid Nicola J. Ronan Yvonne McCarthy Daniel Smith Attila Nagy Elizabeth Joseloff György Balla János Kappelmayer Milan Macek Scott C. Bell Barry J. Plant Margarida D. Amaral István Balogh 《Journal of cystic fibrosis》2019,18(2):271-277
Background
We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.Methods
In this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1–6?months after commencement of ivacaftor, and were correlated with FEV1 (% predicted), sweat chloride, C-reactive protein (CRP) and body mass index (BMI).Results
After 1?month of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6?months. A significant inverse correlation between absolute and delta values of HE4 and FEV1 (r?=??0.5376; P?<?.001 and r?=??0.3285; P?<?.001), was retrospectively observed in pooled groups, including an independent association of HE4 with FEV1 by multiple regression analysis (β?=??0.57, P?=?.019). Substantial area under the receiver operating characteristic curve (ROC-AUC) value was determined for HE4 when 7% mean change of FEV1 (0.722 [95% CI 0.581–0.863]; P?=?.029) were used as classifier, especially in the first 2?months of treatment (0.806 [95% CI 0.665–0.947]; P?<?.001).Conclusions
This study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy. 相似文献3.
The interaction of angiotensin II (ANG II) and atrial natriuretic peptide (ANP) on intracellular pH (pHi) and calcium ([Ca2+]i) was investigated in T84 cells (a permanent cell line derived from human colon epithelium) using the fluorescent stains BCECF/AM and Fluo 4/AM, respectively. pHi recovery rate mediated by the Na+/H+ exchanger (NHE) was examined following an NH4Cl pulse. Under control conditions pHi recovered at 0.114±0.005 pH units/min (n=35). ANG II (10–12 or 10–9 M) increased this value, whilst ANG II (10–7 M) decreased it. These effects of ANG II were impaired by simultaneous addition of 1 M or 25 M HOE-694, indicating that the stimulatory and inhibitory effects of ANG II on pHi recovery are mediated in part via the NHE1 and NHE2 isoforms. ANG II increased [Ca2+]i concentration-dependently. ANP (10–6 M) or dimethyl-BAPTA/AM (50 M) blocked the effects of ANG II on [Ca2+]i and on the rate of pHi recovery. Thapsigargin (10–5 M) enhanced the effect of ANG II on [Ca2+]i and reversed its stimulatory effect on the rate of pHi recovery to an inhibitory one. External Ca2+-free solution did not affect the effects of ANG II on these parameters. These data suggest that the [Ca2+]i increase induced by ANG II is dependent on intracellular calcium stores. They are compatible with the demonstration of two sites on the C-terminal of the Na+/H+ exchanger, one stimulating Na+/H+ activity by increases of [Ca2+]i in the lower range (at 10–12 or 10–9 M ANG II) and the other inhibiting this activity at high [Ca2+]i levels (at 10–7 M ANG II). ANP or dimethyl-BAPTA/AM, by impairing the pathway mediating the increase in [Ca2+]i, block both the stimulatory and inhibitory effects of ANG II. 相似文献
4.
Distinct Leishmania braziliensis isolates induce different paces of chemokine expression patterns 总被引:1,自引:0,他引:1 下载免费PDF全文
Teixeira MJ Fernandes JD Teixeira CR Andrade BB Pompeu ML Santana da Silva J Brodskyn CI Barral-Netto M Barral A 《Infection and immunity》2005,73(2):1191-1195
Inflammatory events during Leishmania braziliensis infection in mice were investigated. Large lesions were directly correlated with the inflammatory reaction but not with parasite burden. Different L. braziliensis strains induce different paces of chemokine expression patterns, leading to diverse cell recruitment and differential inflammatory responses. 相似文献
5.
Patricia Ruiz-Iglesias Abril Gorgori-Gonzlez Maln Massot-Cladera Margarida Castell Francisco J. Prez-Cano 《Nutrients》2021,13(4)
Flavonoids are attracting increasing attention due to their antioxidant, cardioprotective, and immunomodulatory properties. Nevertheless, little is known about their role in exercise performance in association with immune function. This systematic review firstly aimed to shed light on the ergogenic potential of flavonoids. A search strategy was run using SCOPUS database. The returned studies were screened by prespecified eligibility criteria, including intervention lasting at least one week and performance objectively quantified, among others. Fifty-one studies (54 articles) met the inclusion criteria, involving 1288 human subjects, either physically untrained or trained. Secondly, we aimed to associate these studies with the immune system status. Seventeen of the selected studies (18 articles) assessed changes in the immune system. The overall percentage of studies reporting an improved exercise performance following flavonoid supplementation was 37%, the proportion being 25% when considering quercetin, 28% for flavanol-enriched extracts, and 54% for anthocyanins-enriched extracts. From the studies reporting an enhanced performance, only two, using anthocyanin supplements, focused on the immune system and found certain anti-inflammatory effects of these flavonoids. These results suggest that flavonoids, especially anthocyanins, may exert beneficial effects for athletes’ performances, although further studies are encouraged to establish the optimal dosage and to clarify their impact on immune status. 相似文献
6.
Joana Costa Vieira Antnio de O. Mendes Marcelo Leite Ribeiro Andr Costa Vieira Ana Margarida Carta Paulo Torro Fiadeiro Ana Paula Costa 《Materials》2022,15(12)
Embossing is a converting process in which the surface of a tissue paper sheet is changed under high pressure, allowing different functions. In this work, the authors intend to study how the embossing pressure affects the main properties of tissue paper, using a laboratory embossing system. An optimum pressure was achieved at 2.8 bar to this embossing laboratory set-up. The effect of pressure when densifying the paper sheet gives it a gain in mechanical strength but no differences in terms of liquid absorbency. The two embossing patterns present different behaviors but both evidence losses in mechanical and softness properties. On the other hand, the finite element method (FEM) does not show clear evidence of how the pressure affects the paper strength. For the deco die, it is possible to observe that the amount of yielding is slightly higher for lower pressure (2.4 bar), but this plasticity state parameter is very similar for 2.8 bar and 3.2 bar. For the micro die, FEM simulations of the manufacturing pressure do not show a considerable impact on the amount of plasticity state of the material; only for 3.2 bar, it shows a change in the pattern of the plasticity state of the paper during the embossing processes. In the end, to achieve a final product with excellent quality, it is important to make a compromise between the various properties. 相似文献
7.
Borges A Borges M Fernandes J Nascimento H Sameiro-Faria M Miranda V Reis F Belo L Costa E Santos-Silva A 《Renal failure》2011,33(2):138-143
End-stage renal disease (ESRD) under hemodialyses (HD) is related with a higher propensity to infections, essentially due to T-cell lymphopenia. We postulated that HD procedure affects CD4(+) T cells, especially by inducing apoptotic death and that recombinant human erythropoietin (rhEPO) therapy may also play an important role in the modulation of the immune system in these patients. T-cell phenotype and apoptosis of HD patients and healthy controls were evaluated by flow cytometry using anticoagulated whole-blood samples. In 12 HD patients, these parameters were also analyzed before and immediately after HD procedure. HD patients showed a decrease in total circulating CD3(+) lymphocytes, especially in CD4(+) T cells (0.747 ± 0.410 vs. 0.941 ± 0.216 × 10(9)/L, p < 0.05), which could be a consequence of the higher proportion of CD3(+) and CD4(+) lymphocytes in the latest stage of apoptosis (or death) and of the higher proportion of apoptotic CD4(+) T cells observed in the patients immediately after HD procedure (2.91 ± 0.780 vs. 3.90 ± 1.96, p < 0.05). A positive and statistically significant correlation between CD3(+) and CD4(+) lymphocytes in latest stage of apoptosis (or death) with HD time was found (CD3(+): r = 0.592, p < 0.01; CD4(+): r = 0.501, p < 0.01). We also found a negative and significant correlation between weekly rhEPO doses and the number of CD4(+) T cells (r = -0.358, p < 0.05). In conclusion, HD procedure still contributes to the development of T-cell lymphopenia, at least in part, by apoptosis induction. It was also shown that rhEPO therapy is associated with the CD4(+) T-cell decline, possibly by immune modulation, eliminating atypical cells and helping to restore the CD4(+) T-cell subset. 相似文献
8.
Rui Caetano-Oliveira Marcos António Gomes Ana Margarida Abrantes Edgar Tavares-Silva Marco Carvalho Oliveira Mafalda Laranjo Débora Basílio Queirós João Casalta-Lopes Salomé Pires Lina Carvalho Rosa Gouveia Paulo Rodrigues Santos Denise Gonçalves Priolli José Guilherme Tralhão Maria Filomena Botelho 《Pathophysiology》2018,25(2):89-99
Colorectal cancer (CRC) is the second most frequent and fatal cancer in Western countries. Understanding its biology with different incidence along the colon and rectum, genetic profile and how these factors contribute to local/distant progression, has been hampered by the lack of a suitable CRC model.We report a reproducible model, using human CRC cell lines (CL) (WiDr, LS1034, C2BBe1) injected (1?×?107 cells/animal) in RNU rats (n?=?55) which underwent cecostomy and descending colostomy with mucosal-cutaneous fistula of the sigmoid colon. CL were characterized by immunohistochemistry: CK20, CDX2, P53, vimentin, Ki67, CD44, CD133, E-cadherin, β-catenin and CEA; cancer stem cells-immune system interaction was studied and tumor progression was assessed with nuclear medicine imaging (99mTc-MIBI).Animals developed locally invasive tumors and with WiDr neural invasion was registered. Cancer stem cells were detected in WiDr (CD44 positive). All the cell lines stimulated the immune system, being WiDr the most aggressive. Imaging studies demonstrated tumor uptake.With this CRC model we can study the microenvironment role and tumor-stroma interactions. All CL developed primary disease, but only the WiDR established neural invasion which may represent a metastatic pathway. This model can help unveiling the underlying metastatic mechanisms, and ultimately test better therapeutic approaches for CRC. 相似文献
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Metronomic treatment in immunocompetent preclinical GL261 glioblastoma: effects of cyclophosphamide and temozolomide 下载免费PDF全文
Laura Ferrer‐Font Nuria Arias‐Ramos Silvia Lope‐Piedrafita Margarida Julià‐Sapé Martí Pumarola Carles Arús Ana Paula Candiota 《NMR in biomedicine》2017,30(9)
Glioblastoma (GBM) causes poor survival in patients even when applying aggressive treatment. Temozolomide (TMZ) is the standard chemotherapeutic choice for GBM treatment, but resistance always ensues. In previous years, efforts have focused on new therapeutic regimens with conventional drugs to activate immune responses that may enhance tumor regression and prevent regrowth, for example the “metronomic” approaches. In metronomic scheduling studies, cyclophosphamide (CPA) in GL261 GBM growing subcutaneously in C57BL/6 mice was shown not only to activate antitumor CD8+ T‐cell response, but also to induce long‐term specific T‐cell tumor memory. Accordingly, we have evaluated whether metronomic CPA or TMZ administration could increase survival in orthotopic GL261 in C57BL/6 mice, an immunocompetent model. Longitudinal in vivo studies with CPA (140 mg/kg) or TMZ (range 140–240 mg/kg) metronomic administration (every 6 days) were performed in tumor‐bearing mice. Tumor evolution was monitored at 7 T with MRI (T2‐weighted, diffusion‐weighted imaging) and MRSI‐based nosological images of response to therapy. Obtained results demonstrated that both treatments resulted in increased survival (38.6 ± 21.0 days, n = 30) compared with control (19.4 ± 2.4 days, n = 18). Best results were obtained with 140 mg/kg TMZ (treated, 44.9 ± 29.0 days, n = 12, versus control, 19.3 ± 2.3 days, n = 12), achieving a longer survival rate than previous group work using three cycles of TMZ therapy at 60 mg/kg (33.9 ± 11.7 days, n = 38). Additional interesting findings were, first, clear edema appearance during chemotherapeutic treatment, second, the ability to apply the semi‐supervised source analysis previously developed in our group for non‐invasive TMZ therapy response monitoring to detect CPA‐induced response, and third, the necropsy findings in mice cured from GBM after high TMZ cumulative dosage (980–1400 mg/kg), which demonstrated lymphoma incidence. In summary, every 6 day administration schedule of TMZ or CPA improves survival in orthotopic GL261 GBM with respect to controls or non‐metronomic therapy, in partial agreement with previous work on subcutaneous GL261. 相似文献