全文获取类型
收费全文 | 3062篇 |
免费 | 123篇 |
国内免费 | 10篇 |
专业分类
耳鼻咽喉 | 129篇 |
儿科学 | 43篇 |
妇产科学 | 73篇 |
基础医学 | 420篇 |
口腔科学 | 32篇 |
临床医学 | 239篇 |
内科学 | 978篇 |
皮肤病学 | 12篇 |
神经病学 | 221篇 |
特种医学 | 73篇 |
外科学 | 395篇 |
综合类 | 26篇 |
预防医学 | 124篇 |
眼科学 | 38篇 |
药学 | 241篇 |
中国医学 | 3篇 |
肿瘤学 | 148篇 |
出版年
2024年 | 3篇 |
2023年 | 24篇 |
2022年 | 86篇 |
2021年 | 303篇 |
2020年 | 63篇 |
2019年 | 88篇 |
2018年 | 121篇 |
2017年 | 68篇 |
2016年 | 92篇 |
2015年 | 103篇 |
2014年 | 114篇 |
2013年 | 168篇 |
2012年 | 230篇 |
2011年 | 239篇 |
2010年 | 119篇 |
2009年 | 86篇 |
2008年 | 180篇 |
2007年 | 210篇 |
2006年 | 216篇 |
2005年 | 182篇 |
2004年 | 172篇 |
2003年 | 154篇 |
2002年 | 113篇 |
2001年 | 12篇 |
2000年 | 6篇 |
1999年 | 5篇 |
1998年 | 9篇 |
1997年 | 5篇 |
1996年 | 2篇 |
1994年 | 4篇 |
1993年 | 1篇 |
1990年 | 2篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有3195条查询结果,搜索用时 15 毫秒
81.
This paper presents the results of experimental research on the strength properties of porous structures with different degrees of density manufactured of Ti6Al4V titanium alloy by Laser Power Bed Fusion. In the experiment, samples with diamond structure of porosity: 34%, 50%, 73% and 81% were used, as well as samples with near-zero porosity. Monotonic tensile tests were carried out to determine the effective values of axial modulus of elasticity, ultimate tensile strength, offset yield strength, ultimate elongation and Poisson ratio for titanium alloys with different porosities. The paper also proposes relationships that can be easily used to estimate the strength and rigidity of a porous material manufactured by 3D printing. They were obtained by the approximation of two quotients. The first one refers to the relationship between the tensile strength of a material with a defined porosity to the strength of full-filled material. The second similarly determines the change in the value of the axial modulus of elasticity. The analysis of microscopic observations of fracture surfaces and also microtomography visualization of the material structure are also presented. 相似文献
82.
Ewelina Kosicka Marek Borowiec Marcin Kowalczuk Aneta Krzyzak Robert Szczepaniak 《Materials》2020,13(23)
In this research, an analysis of polymer composite with the matrix of L285-cured hardener H286 and six reinforcement layers of carbon fabric GG 280 T was provided. It involved a comparison of the dynamical behavior responses for three cases of composite structures in the context of the presence of the mass share modifier. The samples with the addition of a physical modifier with varying mass percentages were investigated by being subjected to dynamic tests with specific parameters, i.e., constant excitation amplitude and vibration frequency in the vicinity of the base resonance zone. The analysis allowed for indicating the relationship between the composition of the prepared composites and their dynamic response via stiffness characteristics. In addition, the investigation resulted in determining the range of harmful dynamical operating conditions, which may contribute to damage to the composite structures. 相似文献
83.
Marcin Sikora Anna Bajorek Artur Chrobak Jzef Deniszczyk Grzegorz Zikowski Grayna Chekowska 《Materials》2020,13(23)
We report on the comprehensive experimental and theoretical studies of magnetic and electronic structural properties of the Gd0.4Tb0.6Co2 compound crystallization in the cubic Laves phase (C15). We present new results and compare them to those reported earlier. The magnetic study was completed with electronic structure investigations. Based on magnetic isotherms, magnetic entropy change (ΔSM) was determined for many values of the magnetic field change (Δμ0H), which varied from 0.1 to 7 T. In each case, the ΔSM had a maximum around room temperature. The analysis of Arrott plots supplemented by a study of temperature dependency of Landau coefficients revealed that the compound undergoes a magnetic phase transition of the second type. From the M(T) dependency, the exchange integrals between rare-earth R-R (JRR), R-Co (JRCo), and Co-Co (JCoCo) atoms were evaluated within the mean-field theory approach. The electronic structure was determined using the X-ray photoelectron spectroscopy (XPS) method as well as by calculations using the density functional theory (DFT) based Full Potential Linearized Augmented Plane Waves (FP-LAPW) method. The comparison of results of ab initio calculations with the experimental data indicates that near TC the XPS spectrum collects excitations of electrons from Co3d states with different values of exchange splitting. The values of the magnetic moment on Co atoms determined from magnetic measurements, estimated from the XPS spectra, and results from ab initio calculations are quantitatively consistent. 相似文献
84.
Michał Szpinda Waldemar Siedlaczek Anna Szpinda Alina Woźniak Celestyna Mila-Kierzenkowska Marcin Wiśniewski 《Surgical and radiologic anatomy : SRA》2014,36(8):813-820
Purpose
The prenatal assessment of lung volume is becoming increasingly important in determining survival in both preterm infants and newborns affected by pulmonary hypoplasia. This study aimed to examine the lung volumes in the human fetus at varying gestational ages.Materials and methods
Using anatomical, hydrostatic (water displacement according to Archimedes’ patent) and statistical methods (one-way ANOVA test for paired data and post-hoc Bonferroni test, Kolmogorov–Smirnov test, Levene’s test, Student’s t test, regression analysis), volumes of the right and left lungs were measured in 67 human fetuses of both sexes (35 males, 32 females) aged 16–25 weeks, derived from spontaneous abortions and stillbirths.Results
No male–female differences concerning the right and left pulmonary volumes were found. The mean volume of the right lung increased from 1.43 ± 0.25 to 8.45 ± 2.66 cm3, according to the cubic function y = –1.592 + 0.0007 × age3 ± 0.851 (R 2 = 0.84). The volumetric growth of the left lung, from 1.24 ± 0.22 to 6.78 ± 3.03 cm3, followed the cubic model y = –1.110 + 0.0005 × age3 ± 0.794 (R 2 = 0.78). The total pulmonary volume increased from 2.67 ± 0.47 to 15.22 ± 5.58 cm3, in accordance with the cubic model y = –2.729 + 0.0012 × age3 ± 1.598 (R 2 = 0.83). The mean volumes of the right and left lungs accounted for 54.9 ± 2.0 and 45.1 ± 2.0 %, respectively, of the total lung volume.Conclusions
No sex differences are found between the lung volumes in the fetus. The growth of fetal lung volume follows a three-degree polynomial function. Throughout the analyzed period the two lungs grow proportionately to each other, with the volumetric predominance of the right lung. The lung volumes in the fetus are of great relevance in the evaluation of the normal pulmonary growth and the diagnosis of pulmonary hypoplasia. 相似文献85.
A. Moniuszko J. Dunaj I. Święcicka G. Zambrowski J. Chmielewska-Badora W. Żukiewicz-Sobczak J. Zajkowska P. Czupryna M. Kondrusik S. Grygorczuk R. Swierzbinska S. Pancewicz 《European journal of clinical microbiology & infectious diseases》2014,33(10):1835-1841
The purpose of this study was evaluation of the prevalence of co-infection with Borrelia species, A. phagocytophilum and Babesia spp. in patients with tick-borne encephalitis (TBE). At total of 110 patients with TBE were included in the study. Serological tests for tick-borne encephalitis virus (TBEV), PCR for Borrelia species, Anaplasma phagocytophilum and Babesia spp., blood smears for A. phagocytophilum and Babesia spp. and BLAST analysis for Babesia spp. were performed. Results showed a significant majority of patients co-infected with Borrelia species (30/110; 27 %), much less with A. phagocytophilum (12/110; 10.9 %) and with Babesia spp. (1/110; 0.9 %). The BLAST analysis of the 18S rDNA sequence obtained with the Babesia spp. specific primers indicated that the patient was infected with Babesia microti. Triple co-infections (TBEV-Borrelia species- A. phagocytophilum) were observed in three (3/110; 2.7 %) patients. Conclusions were such that differential diagnosis in patients after the tick bite, presenting with acute symptoms, should include not only TBE and Lyme disease, but also other diseases transmitted by ticks. In patients with low parasitemia in suspicion of Babesia spp. infection PCR seems to be a more sensitive method than blood smear. Co-infection with various tick-borne pathogens must be always considered, especially in endemic regions. 相似文献
86.
Natalia Ziętara Marcin Łyszkiewicz Andreas Krueger Siegfried Weiss 《European journal of immunology》2014,44(1):23-32
An appropriate immune response against a specific pathogen requires finely orchestrated interactions between the various cell populations within the immune system. At the same time, immunological tolerance to self must be maintained. DCs play an essential role in achieving these dual requisites. They coordinate adaptive immunity by integrating signals directly emanating from both infectious agents and cells of the immune system. Many such signals, especially those from innate cells and T cells, have been extensively characterized. In contrast, little is known about how B cells modulate function of DCs. B cells produce a variety of cytokines, including IL‐10 and IL‐6, which are known to influence DC function. In addition, Igs constitute the major secretory products of terminally differentiated B cells (plasma cells). DCs express various types of receptors for binding Ig, such as Fc receptors and C‐type lectin receptors. In accordance, Igs can regulate DC function depending on the receptors engaged. Here, we review the emerging immunomodulatory role of cytokines and Ig secreted by B cells. We discuss the evidence for how these B‐cell‐derived factors may shape the adaptive immune response by directly acting on DCs. 相似文献
87.
Malgorzata Gorska Ciebiada Marcin Barylski Maciej Ciebiada 《Inflammation research》2014,63(3):191-195
Background
Because antileukotrienes may inhibit inflammation, it is plausible that montelukast administered for a long time could suppress skin wheal and flare reaction, and thus, it should be discarded prior to the tests. This study assessed the effect of long-lasting treatment with montelukast alone or in combination with antihistamines on wheal and flare in skin pricks tests (SPT) in patients sensitized to perennial allergens.Methods
We conducted a 32-week, double-blind, placebo-controlled, cross-over and randomized trial that implicated two arms: arm A, 20 patients received levocetirizine, montelukast with or without levocetirizine or placebo; arm B, 20 patients received desloratadine, montelukast with or without desloratadine or placebo. All treatment periods lasted 6 weeks and were separated by 2-week washouts. At baseline and on the last day of each treatment period, SPT were performed in all participants.Results
Both levocetirizine and desloratadine in monotherapy, or in combination with montelukast, were effective in reducing wheal and flare in SPT. Monotherapy with montelukast did not change the size of the wheal for either histamine or for house dust mites, in either arm of the study, but significantly reduced the size of flare for histamine in arm A. Addition of montelukast to antihistamine did not exceed efficacy of monotherapy with antihistamine in both arms of the study.Conclusions
Since the size of wheal determines the results of SPT, montelukast, even taken for a long time, does not have to be discarded prior to the tests. 相似文献88.
Agnieszka Zagrska Anna Partyka Adam Bucki Marcin Koaczkowski Magdalena Jastrzbska‐Wisek Anna Czopek Agata Siwek Monika Guch‐Lutwin Marek Bednarski Marek Bajda Jakub Joczyk Kamil Piska Paulina Koczurkiewicz Anna Wesoowska Maciej Pawowski 《Chemical biology & drug design》2019,93(4):511-521
A series of 2‐pyrimidinyl‐piperazinyl‐alkyl derivatives of 1H‐imidazo[2,1‐f]purine‐2,4(3H,8H)‐dione has been synthesized in an attempt to discover a new class of psychotropic agents. Compounds were evaluated for their in vitro affinity for serotonin 5‐HT1A, 5‐HT7, and phosphodiesterases PDE4 and PDE10. The most potent compound 2‐pyrimidinyl‐1‐piperazinyl‐butyl‐imidazo[2,1‐f]purine‐2,4‐dione ( 4b ) behaved as strong and selective antagonist of 5‐HT1A. Molecular modeling studies revealed differences in binding mode between compound 4b and buspirone, which might reflect variation of the ligands’ affinity and potency in the 5‐HT1A receptor. Compound 4b in silico models demonstrated drug‐likeness properties and, contrary to buspirone, showed a metabolic stability in mouse liver microsomes system. Experimentally obtained value of apparent permeability coefficient Papp for 4b in parallel artificial permeability assay indicates the possibility of binding weakly to plasma proteins and high intestinal absorption fraction. Evaluation of the antidepressant‐ and anxiolytic‐like activities of 4b revealed both activities at the same dose of 1.25 mg/kg and seemed to be specific. The antidepressant and/or anxiolytic properties of 4b may be related to its first‐pass effect. 相似文献
89.
90.
Tanaz Sharifnia Victor Rusu Federica Piccioni Mukta Bagul Marcin Imielinski Andrew D. Cherniack Chandra Sekhar Pedamallu Bang Wong Frederick H. Wilson Levi A. Garraway David Altshuler Todd R. Golub David E. Root Aravind Subramanian Matthew Meyerson 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(52):18661-18666
Lung adenocarcinomas harboring activating mutations in the epidermal growth factor receptor (EGFR) represent a common molecular subset of non-small cell lung cancer (NSCLC) cases. EGFR mutations predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs) and thus represent a dependency in NSCLCs harboring these alterations, but the genetic basis of EGFR dependence is not fully understood. Here, we applied an unbiased, ORF-based screen to identify genetic modifiers of EGFR dependence in EGFR-mutant NSCLC cells. This approach identified 18 kinase and kinase-related genes whose overexpression can substitute for EGFR in EGFR-dependent PC9 cells, and these genes include seven of nine Src family kinase genes, FGFR1, FGFR2, ITK, NTRK1, NTRK2, MOS, MST1R, and RAF1. A subset of these genes can complement loss of EGFR activity across multiple EGFR-dependent models. Unbiased gene-expression profiling of cells overexpressing EGFR bypass genes, together with targeted validation studies, reveals EGFR-independent activation of the MEK-ERK and phosphoinositide 3-kinase (PI3K)-AKT pathways. Combined inhibition of PI3K-mTOR and MEK restores EGFR dependence in cells expressing each of the 18 EGFR bypass genes. Together, these data uncover a broad spectrum of kinases capable of overcoming dependence on EGFR and underscore their convergence on the PI3K-AKT and MEK-ERK signaling axes in sustaining EGFR-independent survival.The term “oncogene addiction” has been used to describe the phenomenon whereby tumor cells exhibit singular reliance on an oncogene or oncogenic pathway for their survival, despite the accumulation of multiple genetic lesions (1). In non-small cell lung cancer (NSCLC), this principle is perhaps best exemplified with the finding that epidermal growth factor receptor (EGFR) mutations predict response to EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib, and thus represent a dependency in the subset of tumors harboring these alterations (2–6). However, though EGFR-mutant NSCLCs typically respond dramatically to EGFR TKIs, clinical responses are not universal, even within this genetically defined cohort, with the rate of objective response estimated to be ∼71% (5, 6). Furthermore, the overwhelming majority of patients who initially respond to EGFR inhibitors ultimately develop resistance to therapy (7). A deeper understanding of the genetic underpinnings of EGFR addiction, and how EGFR-mutant cells can overcome reliance on EGFR, may improve clinical outcomes.Here, we have applied an unbiased screening approach to identify genetic modifiers of EGFR dependence in NSCLC. Mounting evidence supports the existence of several genetic modifiers of EGFR dependence in EGFR-mutant NSCLC, which can reduce the degree to which these tumors rely on EGFR and thereby contribute to EGFR TKI resistance (8). Examples include amplification of the MET receptor tyrosine kinase (RTK) (9), activation of the NF-κB pathway (8), amplification of the HER2 (ERBB2) RTK (10), amplification of the CRKL gene (11), and activation of the AXL kinase (12). Notably, MET bypass can be reciprocally achieved via EGFR activation in MET-dependent cells (13), and analogous examples of reciprocal kinase switching have been reported in other kinase-driven cancer models (14, 15). These and other findings suggest that compensatory kinase switching may be a more general way in which oncogene-dependent cancers overcome reliance on their primary driver kinase (14, 16), but the full-range of kinases capable of mediating EGFR bypass has not been systematically studied.Recent advances in large-scale functional genetic libraries have made it possible to query a wide range of genetic perturbations for their ability to modulate specific cellular phenotypes in mammalian systems (17, 18). Using the model of EGFR-mutant, erlotinib-sensitive NSCLC cells, we have performed a systematic ORF-based screen to identify kinase and kinase-related genes whose overexpression can complement loss of EGFR activity in an EGFR-dependent context. Our findings indicate broad potential for EGFR substitution in the setting of EGFR dependence, with compensatory mechanisms commonly conferring EGFR-independent activation of the PI3K-AKT and MEK-ERK signaling pathways. Importantly, this approach has recovered known mechanisms of erlotinib resistance as well as identified novel mediators of EGFR bypass in EGFR-mutant NSCLC. These data support the idea that the EGFR-dependent state can be redundantly driven by diverse genetic inputs that commonly converge on shared downstream signaling nodes. 相似文献