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61.
Witold W. Kilarski Angelika Muchowicz Malgorzata Wachowska Renata Mężyk-Kopeć Jakub Golab Melody A. Swartz Patrycja Nowak-Sliwinska 《Angiogenesis》2014,17(2):347-357
Lymphatic vessels transport fluid, antigens, and immune cells to the lymph nodes to orchestrate adaptive immunity and maintain peripheral tolerance. Lymphangiogenesis has been associated with inflammation, cancer metastasis, autoimmunity, tolerance and transplant rejection, and thus, targeted lymphatic ablation is a potential therapeutic strategy for treating or preventing such events. Here we define conditions that lead to specific and local closure of the lymphatic vasculature using photodynamic therapy (PDT). Lymphatic-specific PDT was performed by irradiation of the photosensitizer verteporfin that effectively accumulates within collecting lymphatic vessels after local intradermal injection. We found that anti-lymphatic PDT induced necrosis of endothelial cells and pericytes, which preceded the functional occlusion of lymphatic collectors. This was specific to lymphatic vessels at low verteporfin dose, while higher doses also affected local blood vessels. In contrast, light dose (fluence) did not affect blood vessel perfusion, but did affect regeneration time of occluded lymphatic vessels. Lymphatic vessels eventually regenerated by recanalization of blocked collectors, with a characteristic hyperplasia of peri-lymphatic smooth muscle cells. The restoration of lymphatic function occurred with minimal remodeling of non-lymphatic tissue. Thus, anti-lymphatic PDT allows control of lymphatic ablation and regeneration by alteration of light fluence and photosensitizer dose. 相似文献
62.
Malgorzata Gawel MD PhD Elzbieta Szmidt‐Salkowska MD PhD Anna Lusakowska MD PhD Monika Nojszewska MD PhD Anna Sulek MSc PhD Wioletta Krysa MSc PhD Marta Rajkiewicz MSc PhD Andrzej Seroka TECH Anna M. Kaminska MD PhD 《Muscle & nerve》2014,49(2):277-283
Introduction: Standard electromyography (EMG) is useful in the diagnosis of myotonic dystrophy type 1 (DM1) and type 2 (DM2), but it does not differentiate between them. The aim of this study was to estimate the utility of the short exercise test (SET) and short exercise test with cooling (SETC) in differentiating between DM1 and DM2. Methods: SET and SETC were performed in 32 patients with DM1 (mean age 35.8 ± 12.7 years) and 28 patients with DM2 (mean age 44.5 ± 12.5 years). Results: We observed a significant decline in compound motor action potential (CMAP) amplitude in DM1 with both SET and SETC immediately after effort. In DM2, there was no marked change in CMAP amplitude with either SET or SETC. Conclusions: SET and SETC may serve as useful tools for clinical differentiation between DM1 and DM2, and they may be used as a guide for molecular testing. Muscle Nerve 49 : 277–283, 2014 相似文献
63.
Inga Pietka Agata Sakowicz Tadeusz Pietrucha Anna Cichocka-Radwan Malgorzata Lelonek 《Central European Journal of Medicine》2014,9(1):21-27
Introduction
Recently several risk scores have been proposed that, beyond traditional risk factors, also include additional inflammatory biomarkers underlying atherothrombosis. The Reynolds Risk Score (RRS) is a point scale assessing the risk of cardiovascular events over 10 years, which takes into account for the first time high-sensitivity C-reactive protein. The aim of this study was to establish clinical usefulness of RRS in men with stable coronary artery disease and preserved left ventricular systolic function.Material and Methods
In total, 119 symptomatic non-diabetic man (mean age 63.9±9.23) who were directed for an elective coronary arteriography were enrolled in the study. Clinical data were collected including the elevated heart rate ≥70 bpm/min, basic laboratory results, placental growth factor and results of coronary angiography. Patients were analyzed related to RRS: low risk <10% (n=50), moderate risk 10-19% (n=46) and high risk >20% (n=23).Results
Opposite to high RRS patients, in the low risk group more often occurred marginal or none atherosclerotic coronary arteries (13% vs. 44%, P=0.0214). The findings have revealed the relationship between the higher risk score and the lower frequency of marginal or no atherosclerotic coronary arteries (OR=0.19, 95%CI 0.05–0.67).Conclusions
The Reynolds Risk Score appears to be useful in men with stable coronary artery disease and preserved left ventricular systolic function in stratifying the severity of coronary atherosclerosis. 相似文献64.
Markus Duechler Lukasz Peczek Karolina Zuk Izabela Zalesna Arkadiusz Jeziorski Malgorzata Czyz 《Immunobiology》2014
The immune system constitutes an important first-line defence against malignant transformation. However, cancer mediated immunosuppression inactivates the mechanisms of host immune surveillance. Cancer cells shut down anti-cancer immunity through direct cell–cell interactions with leukocytes and through soluble factors, establishing an immunosuppressive environment for unimpeded cancer growth. The composition of the immunosuppressive microenvironment in breast tumours is not well documented. To address this question, selected immunosuppressive factors were analyzed in tumour specimens from 33 breast cancer patients after surgery. The mRNA expression of selected genes was quantified in fresh tumour samples. Tumour infiltrating leukocytes were characterized by flow cytometry to identify regulatory T cells, myeloid derived suppressor cells, and type 2 macrophages. Statistical analysis revealed several interesting correlations between the studied parameters and clinical features. Overall, a surprisingly high degree of heterogeneity in the composition of the immunosuppressive environment was found across all breast cancer samples which adds to the complexity of this disease. The influence of the hypoxia inducible factors (HIFs) on the immune microenvironment was also addressed. The level of HIFs correlated with hormone receptor status and the expression of several immunosuppressive molecules. Targeting HIFs might not only sensitize breast tumours for radiation and chemotherapies but also interfere with cancer immunosuppression. 相似文献
65.
Malgorzata Adamska Agata Leonska-Duniec Natalia Lanocha Bogumila Skotarczak 《Acta parasitologica / Witold Stefański Institute of Parasitology, Warszawa, Poland》2014,59(3):433-441
The free-living amoebae (FLA) may live in the environment and also within other organisms as parasites and then they are called amphizoic. They are potentially pathogenic for humans and animals and are found in water that is a source of infection. The aim of this study was molecular detection and identification of these FLA in natural water bodies in North-Western Poland to evaluate the risk of the pathogenic amoebae infections. We examined surface water samples collected from 50 sites and first, the tolerance thermic test was performed in order to select thermophilic, potentially pathogenic strains. For molecular identification of FLA, regions of 18S rDNA, 16S rDNA and intergenic spacers were amplified. Acanthamoeba T4 and T16 genotypes of 18S rDNA gene and 18S rDNA of H. vermiformis were detected. We identified two variants of Acanthamoeba T4 genotype, two variants of Acanthamoeba T16 genotype and one variant of H. vermiformis. Identification of the T16 genotype and H. vermiformis in water was for the first time in Poland. Additionally, we made attempts to adapt the RLB method for detection and differentiation of FLA species and strains. PCR seems to be more sensitive than RLB hybridization, though. 相似文献
66.
Nicole Birgit Arweiler Malgorzata Pietruska Jan Pietruski Ana Skurska Eva Dolińska Christian Heumann Thorsten Mathias Auschill Anton Sculean 《Clinical oral investigations》2014,18(9):2129-2135
Objective
The use of antibacterial photodynamic therapy (aPDT) additionally to scaling and root planing (SRP) has been shown to positively influence the clinical outcomes. However, at present, it is unknown to what extent aPDT may represent a potential alternative to the use of systemic antibiotics in nonsurgical periodontal therapy in patients with aggressive periodontitis (AP). The aim of this study was to evaluate the outcomes following nonsurgical periodontal therapy and additional use of either aPDT or amoxicillin and metronidazole (AB) in patients with AP.Material and methods
Thirty-six patients with AP displaying at least three sites with pocket depth (PD) ≥6 mm were treated with SRP and either systemic administration of AB for 7 days or with two episodes of aPDT. The following clinical parameters were evaluated at baseline and at 6 months: plaque index (PI), bleeding on probing (BOP), PD, gingival recession (GR) and clinical attachment level (CAL).Results
Thirty-five patients have completed the 6-month evaluation. At 6 months, mean PD was statistically significantly reduced in both groups (from 5.0?±?0.8 to 3.0?±?0.6 mm with AB and from 5.1?±?0.5 to 3.9?±?0.8 mm with aPDT (p?0.001)). AB yielded statistically significantly higher improvements in the primary outcome parameter PD (p?0.001) when compared to aPDT. The number of pockets ≥7 mm was reduced from 141 to 3 after AB (p?0.001) and from 137 to 45 after aPDT (p?=?0.03). Both therapies resulted in statistically significant reductions in all parameters compared to baseline.Conclusion
While both treatments resulted in statistically significant clinical improvements, AB showed statistically significantly higher PD reduction and lower number of pockets ≥7 mm compared to aPDT.Clinical relevance
In patients with AP, the two times application of aPDT in conjunction with nonsurgical periodontal therapy cannot be considered an alternative to the systemic use of amoxicillin and metronidazole. 相似文献67.
Piotr Rozga Damian Kloska Sebastian Pawlak Malgorzata Teska-Kaminska Marlena Galazka Katarzyna Bukato Anna Pieczykolan Albert Jaworski Anna Molga-Kaczmarska Aleksandra Kopacz Bogna Badyra Neli Kachamakova-Trojanowska Olga Zolnierkiewicz Marta Targosz-Korecka Katarzyna Poleszak Michal Szymanik Bartlomiej Zerek Jerzy Pieczykolan Alicja Jozkowicz Anna Grochot-Przeczek 《International journal of cancer. Journal international du cancer》2020,147(4):1117-1130
Targeting of the TRAIL-DR4/5 pathway was proposed as a promising approach for specific induction of apoptosis in cancer cells. Clinical trials, however, showed inadequate efficiency of TRAIL as a monotherapy. It is a widely held view that the application of multifunctional molecules or combination therapy may lead to substantial improvement. Here, we demonstrate the effectiveness and safety of a novel chimeric protein, AD-O51.4, which is a TRAIL equipped with positively charged VEGFA-derived effector peptides. The study was performed in multiple cancer cell line- and patient-derived xenografts. A pharmacokinetic profile was established in monkeys. AD-O51.4 strongly inhibits tumor growth, even leading to complete long-term tumor remission. Neither mice nor monkeys treated with AD-O51.4 demonstrate symptoms of drug toxicity. AD-O51.4 exhibits a satisfactory half-life in plasma and accumulates preferentially in tumors. The cellular mechanism of AD-O51.4 activity involves both cytotoxic effects in tumor cells and antiangiogenic effects on the endothelium. The presence of DRs in cancer cells is crucial for AD-O51.4-driven apoptosis execution. The TRAIL component of the fusion molecule serves as an apoptosis inducer and a cellular anchor for the effector peptides in TRAIL-sensitive and TRAIL-resistant cancer cells, respectively. The FADD-dependent pathway, however, seems to be not indispensable in death signal transduction; thus, AD-O51.4 is capable of bypassing the refractoriness of TRAIL. AD-O51.4-driven cell death, which exceeds TRAIL activity, is achieved due to the N-terminally fused polypeptide, containing VEGFA-derived effector peptides. The high anticancer efficiency of AD-O51.4 combined with its safety has led to the entry of AD-O51.4 into toxicological studies. 相似文献
68.
69.
Borroto-Escuela Dasiel O. Romero-Fernandez Wilber Wydra Karolina Zhou Zilong Suder Agata Filip Malgorzata Fuxe Kjell 《Neurotoxicity research》2020,37(2):433-444
Neurotoxicity Research - Cocaine was previously shown to act at the Sigma1R which is a target for counteracting cocaine actions. It therefore becomes of interest to test if the monoamine stabilizer... 相似文献
70.
Impaired empathy is associated with a variety of psychiatric conditions; however, little is known about the differential relations between certain forms of psychopathology and cognitive and affective empathy in adolescent girls and boys. The aim of this study was to examine the relations between externalizing and internalizing disorders and cognitive and affective empathy, respectively, while controlling for covariance among different forms of psychopathology, separately in girls and boys. A total of 507 inpatient adolescents (319 girls and 188 boys) in the age range of 12–17 years completed the Basic Empathy Scale that measures affective and cognitive empathy. The Youth Self-Report Form and Child Behavior Checklist were used to assess the severity of psychopathological symptoms. Results demonstrated that affective and cognitive empathy were negatively associated with conduct problems only in girls, but not in boys. Affective empathy was positively related to internalizing problems observed by parents and youths and self-reported ADHD symptoms in girls and boys. The clinical implications of these differential relationships for externalizing versus internalizing symptoms and empathy are discussed. 相似文献