全文获取类型
收费全文 | 3763篇 |
免费 | 151篇 |
国内免费 | 21篇 |
专业分类
耳鼻咽喉 | 87篇 |
儿科学 | 54篇 |
妇产科学 | 83篇 |
基础医学 | 597篇 |
口腔科学 | 53篇 |
临床医学 | 304篇 |
内科学 | 844篇 |
皮肤病学 | 44篇 |
神经病学 | 434篇 |
特种医学 | 112篇 |
外科学 | 370篇 |
综合类 | 26篇 |
预防医学 | 202篇 |
眼科学 | 56篇 |
药学 | 429篇 |
中国医学 | 1篇 |
肿瘤学 | 239篇 |
出版年
2022年 | 42篇 |
2021年 | 87篇 |
2020年 | 31篇 |
2019年 | 60篇 |
2018年 | 82篇 |
2017年 | 49篇 |
2016年 | 45篇 |
2015年 | 62篇 |
2014年 | 100篇 |
2013年 | 137篇 |
2012年 | 177篇 |
2011年 | 220篇 |
2010年 | 123篇 |
2009年 | 128篇 |
2008年 | 158篇 |
2007年 | 171篇 |
2006年 | 192篇 |
2005年 | 191篇 |
2004年 | 172篇 |
2003年 | 162篇 |
2002年 | 148篇 |
2001年 | 137篇 |
2000年 | 127篇 |
1999年 | 106篇 |
1998年 | 52篇 |
1997年 | 34篇 |
1996年 | 28篇 |
1995年 | 28篇 |
1994年 | 22篇 |
1993年 | 14篇 |
1992年 | 40篇 |
1991年 | 53篇 |
1990年 | 67篇 |
1989年 | 62篇 |
1988年 | 61篇 |
1987年 | 74篇 |
1986年 | 50篇 |
1985年 | 68篇 |
1984年 | 35篇 |
1983年 | 31篇 |
1982年 | 27篇 |
1981年 | 17篇 |
1980年 | 16篇 |
1979年 | 33篇 |
1978年 | 13篇 |
1977年 | 14篇 |
1974年 | 28篇 |
1973年 | 21篇 |
1972年 | 22篇 |
1971年 | 25篇 |
排序方式: 共有3935条查询结果,搜索用时 15 毫秒
81.
Mutations in the skeletal muscle α-actin gene (ACTA1) cause a range of congenital myopathies characterised by muscle weakness and specific skeletal muscle structural lesions. Actin accumulations, nemaline and intranuclear bodies, fibre-type disproportion, cores, caps, dystrophic features and zebra bodies have all been seen in biopsies from patients with ACTA1 disease, with patients frequently presenting with multiple pathologies. Therefore increasingly it is considered that these entities may represent a continuum of structural abnormalities arising due to ACTA1 mutations. Recently an ACTA1 mutation has also been associated with a hypertonic clinical presentation with nemaline bodies. Whilst multiple genes are known to cause many of the pathologies associated with ACTA1 mutations, to date actin aggregates, intranuclear rods and zebra bodies have solely been attributed to ACTA1 mutations. Approximately 200 different ACTA1 mutations have been identified, with 90 % resulting in dominant disease and 10 % resulting in recessive disease. Despite extensive research into normal actin function and the functional consequences of ACTA1 mutations in cell culture, animal models and patient tissue, the mechanisms underlying muscle weakness and the formation of structural lesions remains largely unknown. Whilst precise mechanisms are being grappled with, headway is being made in terms of developing therapeutics for ACTA1 disease, with gene therapy (specifically reducing the proportion of mutant skeletal muscle α-actin protein) and pharmacological agents showing promising results in animal models and patient muscle. The use of small molecules to sensitise the contractile apparatus to Ca2+ is a promising therapeutic for patients with various neuromuscular disorders, including ACTA1 disease. 相似文献
82.
Ernst Hein Magdalena Nowak Olga Kiess Teresa Biermann Kristina Bayerlein Johannes Kornhuber Thomas Kraus 《Journal of neural transmission (Vienna, Austria : 1996)》2013,120(5):821-827
Invasive vagus nerve stimulation has been demonstrated to be an effective treatment in major depressive episodes. Recently, a novel non-invasive method of stimulating the vagus nerve on the outer canal of the ear has been proposed. In healthy subjects, a prominent fMRI BOLD signal deactivation in the limbic system was found. The present pilot study investigates the effects of this novel technique of auricular transcutaneous electric nerve stimulation in depressed patients for the first time. A total of 37 patients suffering from major depression were included in two randomized sham controlled add-on studies. Patients were stimulated five times a week on a daily basis for the duration of 2 weeks. On days 0 and 14, the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI) were assessed. In contrast to sham-treated patients, electrically stimulated persons showed a significantly better outcome in the BDI. Mean decrease in the active treatment group was 12.6 (SD 6.0) points compared to 4.4 (SD 9.9) points in the sham group. HAMD score did not change significantly in the two groups. An antidepressant effect of a new transcutaneous auricular nerve stimulation technique has been shown for the first time in this controlled pilot study. Regarding the limitations of psychometric testing, the risk of unblinding for technical reasons, and the small sample size, further studies are necessary to confirm the present results and verify the practicability of tVNS in clinical fields. 相似文献
83.
Stern DA Riedler J Nowak D Braun-Fahrlander C Swoboda I Balic N Chen KW Vrtala S Grönlund H van Hage M Valenta R Spitzauer S Von Mutius E Vercelli D 《The Journal of allergy and clinical immunology》2007,119(2):351-358
BACKGROUND: IgE synthesis by human B cells results from allergen-dependent, T(H)2-mediated isotype switching. Exposure to a farming environment protects against IgE responses. OBJECTIVE: We reconstructed allergen-dependent switching patterns in vivo to identify the level or levels at which farm exposure acts to protect against atopy. METHODS: Serum IgG1 to IgG4 and IgE to grass (rPhl p 1 and rPhl p 5), cat (rFel d 1), and mite (rDer p 2) were assessed by means of ELISA in the Allergy and Endotoxin study population (812 children). Farm exposure was defined as currently living on a farm, exposure to stables/farm milk in the first year of life, or both. RESULTS: Farm exposure did not affect allergen-specific IgG2 and IgG3 levels but had complex allergen-specific effects on IgG1, IgG4, and IgE levels. Exposure protected against grass-specific responses at every step along the IgG1/IgG4/IgE switching pathway but had no significant effect on mite responses. Protection from cat responses was concentrated at the IgG1 level. For all allergens, failure to express IgG1 was associated with low prevalence of IgG4 or IgE responses. Notably, coexpression of IgG1, IgG4, and IgE to grass was associated with increased risk of allergic disease and higher IgE levels compared with production of IgG1 and IgE without IgG4, suggesting IgG4 coexpression marks stronger activation of T(H)2-dependent events. CONCLUSION: The protective effects of farm exposure were confined to T(H)2-dependent IgG1, IgG4, and IgE expression and were allergen and switch stage specific, suggesting that distinct mechanisms regulate individual steps within allergen-induced class switching in vivo. CLINICAL IMPLICATIONS: Environmental interventions to prevent IgE expression might need to be tailored to specific allergens. 相似文献
84.
The aim of this study was to characterize the stability of new vehicles for the undecylenoyl phenylalanine that is used as skin-lightening agent in the melasma treatment. The purpose of this research was also to analyse the release kinetics of phenylalanine derivative from topical preparations through different synthetic membranes. Topical formulations such as two different macroemulsions, hydrogels (based on carbomer and hydroxyethylcellulose) and microemulsions were characterized in terms of stability by laser diffraction method. Additionally, multiple light scattering assessed the stability of macroemulsions. The release rates of active substance through different membranes (such as Cuprophan, nitrocellulose, cellulose acetate and Strat-M) were determined using enhancer cell. In order to explain the mechanism of release process the results were fitted with different kinetic models. New stable vehicles for Ude-Phe were successfully obtained. The results proved that the membrane structure had the influence on the release rate of undecylenoyl phenylalanine. The slowest release rate of Ude-Phe was observed when Strat-M membrane was applied. The highest amount of active substance was released from the hydrogel based on carbomer. The release of undecylenoyl phenylalanine from both macroemulsions and hydrogel based on hydroxyethylcellulose followed the Higuchi model. Whereas the release results of Ude-Phe from both microemulsion-based hydrogels and carbomer hydrogel can be described by using Korsmeyer-Peppas model. Hydrogels and microemulsion-based hydrogels could be recommended as proper vehicles for the derivative of phenylalanine. 相似文献
85.
Agnieszka Matuszewska Beata Nowak Diana Jędrzejuk Marcin Landwójtowicz Ewa Sadanowicz Tomasz Sozański Joanna Kwiatkowska Małgorzata Pieśniewska Marek Bolanowski Adam Szeląg 《Pharmacological reports : PR》2018,70(5):951-954
Background
Histamine regulates function of osteoclasts and osteoblasts, however data regarding the influence of histamine H2 receptors antagonists on bone tissue are ambiguous. Factors that influence growing skeleton may have an important impact on the peak bone mass and future risk of fractures. The aim of our study was the assessment of influence of ranitidine, on growing bones.Methods
The experiment was carried out on young male Wistar rats divided into two groups receiving either ranitidine (10 mg/kg ip) or vehicle.Results
A significant decrease in femoral BMD in ranitidine-treated rats (R) compared to vehicle-treated ones (C) was detected (0.262 ± 0.009 g/cm2vs. 0.271 ±0.007 g/cm2, p < 0.05). In group R we observed elevated serum C-terminated telopeptide of type I collagen (CTX) level with concomitantly lowered serum osteocalcin (OC) concentration comparing to control group (151.2 ± 27.2 pg/ml vs. 101.5 ± 55.6, p < 0.05 and 229.1 ± 50.0 pg/ml vs. 292.0 ± 52.9, p < 0.05, respectively). Serum concentration of inorganic phosphorus was lower in group R than in group C (134 ± 13 mmol/L vs. 157 ± 28 mmol/L, p < 0.05).Conclusions
Long-term administration of ranitidine increases bone resorption and decreases bone formation in growing rats leading to decrease in BMD. 相似文献86.
Rabea Hein Hendrik J. Sake Claudia Pokoyski Joachim Hundrieser Antje Brinkmann Wiebke Baars Monika Nowak‐Imialek Andrea Lucas‐Hahn Constanca Figueiredo Hans‐Joachim Schuberth Heiner Niemann Bjrn Petersen Reinhard Schwinzer 《American journal of transplantation》2020,20(4):988-998
Porcine xenografts lacking swine leukocyte antigen (SLA) class I are thought to be protected from human T cell responses. We have previously shown that SLA class I deficiency can be achieved in pigs by CRISPR/Cas9‐mediated deletion of β2‐microglobulin (B2M). Here, we characterized another line of genetically modified pigs in which targeting of the B2M locus did not result in complete absence of B2M and SLA class I but rather in significantly reduced expression levels of both molecules. Residual SLA class I was functionally inert, because no proper differentiation of the CD8+ T cell subset was observed in B2Mlow pigs. Cells from B2Mlow pigs were less capable in triggering proliferation of human peripheral blood mononuclear cells in vitro, which was mainly due to the nonresponsiveness of CD8+ T cells. Nevertheless, cytotoxic effector cells developing from unaffected cell populations (eg, CD4+ T cells, natural killer cells) lysed targets from both SLA class I+ wildtype and SLA class Ilow pigs with similar efficiency. These data indicate that the absence of SLA class I is an effective approach to prevent the activation of human CD8+ T cells during the induction phase of an anti‐xenograft response. However, cytotoxic activity of cells during the effector phase cannot be controlled by this approach. 相似文献
87.
P. Koźlik R. Pfitzner E. Nowak A. Kozynacka Ł. Durajski Ł. Janik P. Przybyłowski 《Transplantation proceedings》2014
Background
Family objection precludes 10% of cadaveric donations in Poland. Academic students represent a socially influential demographic group. Educational campaigns improving their attitudes may increase overall donation rates. The aim of this study was to assess correlations between knowledge, beliefs, and attitudes regarding organ transplantation and the identification of the most critical factors affecting one's donation preferences.Methods
Eight hundred students from 4 public universities in Krakow, Poland, participated in the study; participants were diverse in age, sex, hometown population, and academic discipline (400 medical, 400 non-medical). This cross-sectional study was conducted with the use of a group-administered questionnaire inquiring into demographics, general and professional knowledge, beliefs, and attitudes toward organ transplantation.Results
Attitudes toward organ donation correlate positively with beliefs (ρ = 0.36), general knowledge (ρ = 0.48), and professional knowledge (ρ = 0.23) scores. Beliefs were proven to correlate with general (ρ = 0.21) and professional (ρ = 0.26) knowledge as well. Misconceptions about the medical criteria allowing cadaveric organ recovery, distrust for brain death reliability, fear of “do not resuscitate” approach toward Organ Donor Card holders, a strong belief in organ trafficking, and unawareness of family members' attitudes are the most important factors influencing one's refusal/uncertainty to donate.Conclusions
Knowledge, attitudes, and refusal rates differ, depending on the academic discipline as well as other demographics, indicating a need for a specifically targeted approach in designing educational campaigns. Sources of knowledge are related to donation rates, with pre-academic education evaluated as unfavorable, as opposed to healthcare providers and the media. 相似文献88.
G. Wasilewski P. Przybyłowski L. Janik E. Nowak J. Sadowski J. Małyszko 《Transplantation proceedings》2014
Introduction
Renalase may degrade catecholamines and regulate sympathetic tone and blood pressure. The aim of this study was to assess dopamine, norepinephrine, and renalase in 80 heart transplant recipients and 22 healthy volunteers and their correlations with heart rate, blood pressure control, type of hypotensive therapy, and renal function.Patients and Methods
Renalase, dopamine, and norepinephrine were studied by using commercially available assays.Results
Renalase levels were higher in heart transplant recipients compared with healthy volunteers, and noradrenaline levels were lower in the studied cohort patients than in the healthy volunteers. Noradrenaline was correlated with white blood cell count (r = −0.21, P < .05), copeptin (r = 0.41, P < .01), and left ventricular diameter (r = −0.29, P < .05), whereas dopamine was correlated in univariate analysis with white blood cell count (r = −0.22, P < .05), posterior wall of left ventricular diameter (r = 0.58, P < .01), and left atrium diameter (r = −0.31, P < .05). Neither noradrenaline nor dopamine was correlated with heart rate, blood pressure, kidney function, or New York Heart Association class. Noradrenaline was significantly higher in patients with elevated diastolic blood pressure (>90 mm Hg) compared with those with normal diastolic blood pressure (P < .05). Renalase was related to kidney function but was unrelated to catecholamines.Conclusions
Elevated renalase levels in heart transplant patients were related to kidney function but not linked to the sympathetic nervous system activity in this study population. In heart transplant recipients, these findings might suggest that sympathetic denervation and the modulation of β-receptors persist. 相似文献89.
G. Wasilewski P. Przybylowski L. Janik E. Nowak J. Sadowski J. Malyszko 《Transplantation proceedings》2014
Introduction
Cardiac transplantation is the definitive therapy for eligible patients with end-stage heart failure. Hypertension is a widely accepted risk factor for its outcome.Patients and Methods
We analyzed 169 heart transplant recipients. The diagnosis of hypertension was made on the basis of information gathered at 3 consecutive visits. Complete blood count, urea, serum lipids, fasting glucose, creatinine, and N-terminal pro–B-type natriuretic peptide were also studied.Results
In the orthotopic heart transplantation (OHT) population, 11% had diabetes and 68% had chronic kidney disease. Hypertension was diagnosed and treated in 68% of the OHT patients. Hypertensive patients were significantly older, with a lower estimated glomerular filtration rate and higher serum creatinine and erythrocyte count. Thirty-three percent of patients did not achieve target blood pressure despite optimal medical treatment. Patients treated with tacrolimus had similar systolic blood pressure compared with those treated with cyclosporine (with a tendency to have lower values). Patients treated with mammalian target of rapamycin inhibitors had similar systolic and diastolic blood pressures compared with those treated without these inhibitors. In the group of patients given steroids, systolic and diastolic blood pressures were significantly lower than in the group not treated with steroids. In addition, steroid-treated patients had a significantly lower estimated glomerular filtration rate, hemoglobin, and erythrocyte count and higher serum creatinine, N-terminal pro–B-type natriuretic peptide, and New York Heart Association class. Chronic kidney disease was also more prevalent in this group. Blood pressure was not related to the kidney function.Conclusions
Despite polytherapy, optimal blood pressure control was not achieved in the majority of patients. OHT patients have a high prevalence of hypertension, which should be treated adequately. More efforts should be made to optimize blood pressure control, particularly when other comorbidities are present. Blood pressure was not related to patient kidney function. 相似文献90.
Fibroblast Growth Factor 23 and Klotho as Cardiovascular Risk Factors in Heart Transplant Recipients
P. Przybylowski G. Wasilewski L. Janik S. Kozlowska E. Nowak J. Malyszko 《Transplantation proceedings》2014