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71.
Hardin M Zielinski J Wan ES Hersh CP Castaldi PJ Schwinder E Hawrylkiewicz I Sliwinski P Cho MH Silverman EK 《American journal of respiratory cell and molecular biology》2012,47(2):203-208
We examined the association between single-nucleotide polymorphisms (SNPs) previously associated with chronic obstructive pulmonary disease (COPD) and/or lung function with COPD and COPD-related phenotypes in a novel cohort of patients with severe to very severe COPD. We examined 315 cases of COPD and 330 Caucasian control smokers from Poland. We included three SNPs previously associated with COPD: rs7671167 (FAM13A), rs13180 (IREB2), and rs8034191 (CHRNA 3/5), and four SNPs associated with lung function in a genome-wide association study of general population samples: rs2070600 (AGER), rs11134242 (ADCY2), rs4316710 (THSD4), and rs17096090 (INTS12). We tested for associations with severe COPD and COPD-related phenotypes, including lung function, smoking behavior, and body mass index. Subjects with COPD were older (average age 62 versus 58 years, P < 0.01), with more pack-years of smoking (45 versus 33 pack-years, P < 0.01). CHRNA3/5 (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.5-2.4; P = 7.4 × 10(-7)), IREB2 (OR, 0.69; 95% CI, 0.5-0.9; P = 3.4 × 10(-3)), and ADCY2 (OR, 1.35; 95% CI, 1.1-1.7; P = 0.01) demonstrated significant associations with COPD. FAM13A (OR, 0.8; 95% CI, 0.7-1.0; P = 0.11) approached statistical significance. FAM13A and ADCY2 also demonstrated a significant association with lung function. Thus, in severe to very severe COPD, we demonstrate a replication of association between two SNPs previously associated with COPD (CHRNA3/5 and IREB2), as well as an association with COPD of one locus initially associated with lung function (ADCY2). 相似文献
72.
Lourdusamy A Newhouse S Lunnon K Proitsi P Powell J Hodges A Nelson SK Stewart A Williams S Kloszewska I Mecocci P Soininen H Tsolaki M Vellas B Lovestone S;AddNeuroMed Consortium Dobson R;Alzheimer's Disease Neuroimaging Initiative 《Human molecular genetics》2012,21(16):3719-3726
Proteins are central to almost all cellular processes, and dysregulation of expression and function is associated with a range of disorders. A number of studies in human have recently shown that genetic factors significantly contribute gene expression variation. In contrast, very little is known about the genetic basis of variation in protein abundance in man. Here, we assayed the abundance levels of proteins in plasma from 96 elderly Europeans using a new aptamer-based proteomic technology and performed genome-wide local (cis-) regulatory association analysis to identify protein quantitative trait loci (pQTL). We detected robust cis-associations for 60 proteins at a false discovery rate of 5%. The most highly significant single nucleotide polymorphism detected was rs7021589 (false discovery rate, 2.5 × 10(-12)), mapped within the gene coding sequence of Tenascin C (TNC). Importantly, we identified evidence of cis-regulatory variation for 20 previously disease-associated genes encoding protein, including variants with strong evidence of disease association show significant association with protein abundance levels. These results demonstrate that common genetic variants contribute to the differences in protein abundance levels in human plasma. Identification of pQTLs will significantly enhance our ability to discover and comprehend the biological and functional consequences of loci identified from genome-wide association study of complex traits. This is the first large-scale genetic association study of proteins in plasma measured using a novel, highly multiplexed slow off-rate modified aptamer (SOMAmer) proteomic platform. 相似文献
73.
Behavioural and psychological symptoms of dementia (BPSD) are present in the course of the illness in up to 90% of patients with Alzheimer''s disease (AD). They are the main source of caregiver burden and one of the major factors contributing to early institutionalization. The involvement of a genetic component in BPSD aetiology seems beyond controversy, though the exact significance of particular polymorphisms is uncertain in the majority of cases. Multiple genes have been assessed for their putative influence on BPSD risk. In this paper we review the behavioural genetics of AD, particularly the importance, with respect to BPSD risk, of genes coding for apolipoprotein E and proteins involved in the process of neurotransmission: serotonin receptors, serotonin transporter, COMT, MAO-A, tryptophan hydroxylase and dopamine receptors. A general conclusion is the striking inconsistency of the findings, unsurprising in the field of psychiatric genetics. The potential reasons for such discrepancy are exhaustively discussed. 相似文献
74.
Kurt Schilling Yurui Gao Vaibhav Janve Iwona Stepniewska Bennett A. Landman Adam W. Anderson 《NMR in biomedicine》2017,30(12)
It is now widely recognized that voxels with crossing fibers or complex geometrical configurations present a challenge for diffusion MRI (dMRI) reconstruction and fiber tracking, as well as microstructural modeling of brain tissues. This “crossing fiber” problem has been estimated to affect anywhere from 30% to as many as 90% of white matter voxels, and it is often assumed that increasing spatial resolution will decrease the prevalence of voxels containing multiple fiber populations. The aim of this study is to estimate the extent of the crossing fiber problem as we progressively increase the spatial resolution, with the goal of determining whether it is possible to mitigate this problem with higher resolution spatial sampling. This is accomplished using ex vivo MRI data of the macaque brain, followed by histological analysis of the same specimen to validate these measurements, as well as to extend this analysis to resolutions not yet achievable in practice with MRI. In both dMRI and histology, we find unexpected results: the prevalence of crossing fibers increases as we increase spatial resolution. The problem of crossing fibers appears to be a fundamental limitation of dMRI associated with the complexity of brain tissue, rather than a technical problem that can be overcome with advances such as higher fields and stronger gradients. 相似文献
75.
Iwona Stelmach Katarzyna Smejda Joanna Jerzynska W?odzimierz Stelmach Pawel Majak Piotr Stelmach Piotr Kuna 《Annals of allergy, asthma & immunology》2007,99(2):170-177
BACKGROUND: Several risk factors for the development of asthma and atopic disease in children have been described. Furthermore, there is consistent evidence that the prevalence of atopy increases with higher socioeconomic status. The knowledge about risk factors and preventive factors for atopy needs to be improved. OBJECTIVE: To compare 2 child populations (foster care and reference children) with different risk and protective factors for the development of atopy. METHODS: The study group consisted of 415 children, living in all 10 community foster homes in Lodz, a large industrial city in Poland. The study was performed from April 2, 2004, to April 30, 2006. The reference group consisted of 500 children, living with their parents at home, recruited from primary care centers. The primary outcome measures were skin prick test results and specific IgE in serum. Secondary outcomes included symptoms of allergic diseases and family history, including life conditions in early childhood. RESULTS: The full analysis set included 408 study children and 402 reference children. Significant differences were observed in the prevalence of atopy between the study and reference groups (11.3% vs 25.9%). We observed more positive skin prick test results in children from the reference group than in study children. To explain this phenomenon, we selected 16 variables that differ in both groups in early life and relate these to atopy. We found that the more cumulative features characteristic of the foster home population (poor living conditions), the lower the risk of atopy. CONCLUSION: Extremely unfavorable environmental circumstances, which are characteristic of the foster home population during early childhood, might prevent from atopy. 相似文献
76.
Szatkowska I Szymańska O Bojarski P Grabowska A 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2007,181(1):109-115
Inhibition underlies cognitive processes such as overcoming habitual responses, suppressing of goal-irrelevant information,
and switching of attention between stimuli or task rules. These processes are thought to depend on the frontal lobes. However,
the precise role of the ventral frontal regions (orbitofrontal cortex) in these processes remains elusive. In the present
study, our goal was to clarify the role of the orbitofrontal cortex in cognitive inhibition by examining the effects of focal
lesions to the medial orbitofrontal cortex (posterior part of the gyrus rectus) on performance in tasks that required inhibitory
control. Patients who had undergone surgery for an anterior communicating artery aneurysm and normal control subjects (C)
participated in the study. The patients were subdivided into three groups: those with resection of the left (LGR+) or right
(RGR+) gyrus rectus, and without such a resection (GR-). The Stroop Color-Word test, Trail Making B test, and the Category
test were used as instruments for assessing response inhibition, switching between concrete stimuli, and switching between
abstract task rules, respectively. In addition, the Digit Symbol test was used to examine sustained attention and processing
speed. In the Stroop Color-Word test, the RGR+ group performed worse than all other groups. In the Trail Making B test, the
RGR+ and LGR+ groups performed worse than both the GR- and C groups. In the Category test and Digit Symbol test, the groups
did not differ significantly from each other. Our study indicates a specific contribution of the medial orbitofrontal cortex
to response inhibition and stimulus-based switching of attention. 相似文献
77.
BACKGROUND: Significant research has looked at the psychosocial impairment associated with bipolar I disorder and major depressive disorder. Far less is known about the impact of bipolar II disorder. The present study assessed the social and work impairment associated with bipolar II disorder and whether these are more or less severe than those associated with bipolar I disorder or major depressive disorder. METHODS: Psychiatric outpatients with bipolar II disorder (n=89), bipolar I disorder (n=45) and major depressive disorder (n=1251) were assessed cross-sectionally by highly trained raters using semi-structured interviews. Participants were in a major depressive episode. Groups were compared on a series of indicators of psychosocial functioning. RESULTS: Bipolar I and II disorder were associated with greater absenteeism from work due to psychopathology compared to major depressive disorder. The bipolar disorders also had higher rates of hospitalization and suicide attempts. Bipolar II disorder had fewer hospitalization than bipolar I disorder which may have led to slightly less severe work impairment. Both conditions had similar rates of serious suicide attempts. LIMITATIONS: The study was cross-sectional and retrospective. Furthermore, the sample consisted of outpatients seeking treatment, limiting generalizability to other settings. CONCLUSION: Bipolar II disorder is associated with serious work impairment and a high number of serious suicide attempts. The level of impairment is more similar than it is different from that associated with bipolar I disorder. Clinicians would be mistaken to presume that the "softer" bipolar spectrum, specifically bipolar II disorder, is less impairing than bipolar I disorder. 相似文献
78.
We describe 3 unusual B-cell non-Hodgkin's lymphomas in which the entire tumors histologically mimicked marginal zone B-cell lymphoma. All patients were male (mean age, 65 years). Excisional biopsy from lymph node (2 of 3) and parotid gland (1 of 3) showed proliferation of monocytoid B-cells with plasmacytoid features (2 of 3) and conspicuous absence of large lymphoma cells (3 of 3). By immunohistochemistry, cyclin D1 was positive (3 of 3), CD23 was negative (3 of 3), and aberrant expression of CD5/CD43 was present in 1 case. Ki67 labeling was greater than 50% in 1 case and 10% to 25% in the other 2 cases. Evidence of the t(11;14) was detectable in all by molecular techniques. One patient died within 15 months, and the other 2 patients had widely disseminated diseases at the last follow-up (8 months). Based on these features, we believed that the best classification for these lesions is the marginal zone B-cell lymphoma-like mantle cell lymphoma. 相似文献
79.
Joanna Sikora Barbara Kostka Iwona Marczyk Urszula Krajewska Maciej Cha?ubiński Marlena Broncel 《Archives of Medical Science》2013,9(4):622-628
Introduction
It is generally assumed that cholesterol reduction by statins is the predominant therapeutic result underlying their beneficial effects in cardiovascular disease. However, the action of statins may be partially independent of their effects on plasma cholesterol levels, as they combine lipid lowering with positive effects on hemorheological conditions and endothelial function. We evaluated the impact of statin treatment on platelet adhesion to fibrinogen (spontaneous and ADP-activated), along with ADP, collagen or ristocetin-induced aggregation in type II hyperlipidemic patients.Material and methods
The study group included 70 persons: 50 patients affected by type II hyperlipidemia without concomitant diseases and 20 healthy volunteers. The effects of 8-week statin treatment (atorvastatin 10 mg/day, simvastatin 20 mg/day, or pravastatin 20 mg/day) on platelet activation were evaluated.Results
Regardless of the type of statin, a significant decrease in ADP-induced platelet aggregation was observed: for atorvastatin 50.6 ±12.8% vs. 41.1 ±15.8% (p < 0.05), for simvastatin 57.2 ±18.0% vs. 44.7 ±22.1% (p = 0.05), and for pravastatin 55.8 ±19.5% vs. 38.8 ±23.3% (p < 0.05). There was no significant effect of statins on collagen or ristocetin-induced platelet aggregation and adhesion.Conclusions
Therapy with statins beneficially modifies ADP-induced platelet aggregation in patients with hyperlipidemia and does not affect spontaneous or ADP-induced platelet adhesion to fibrinogen and platelet aggregation induced by collagen or ristocetin. 相似文献80.
Background:?Menarcheal age is the most important measure of sexual maturation in girls and a sensitive indicator of environmental conditions during childhood.Objective:?The study analysed the association between age at menarche and socio-economic characteristics (urbanization, population size, education of parents and number of children in the family).Subjects and methods:?Questionnaire data were collected from 3271 female schoolchildren born between 1981 and 1984, living in three provinces of southern Poland. Menarcheal age was estimated by the recall method and based on the date of menarche given by the study participants. ANCOVA and multiple regression analyses were applied to test statistical significance of differences between groups.Results:?Girls from families with high socio-economic status experience menarche at an earlier age than girls from families with lower socio-economic status. However, depending on the geographical region and the population size, other factors influence menarcheal age. In the Krakow province, factors that significantly differentiate age at menarche are urbanization, father's education and number of children in the family; in the Opole province, these factors include urbanization and number of children in the family, while in the Nowy Sacz province, number of children in the family is significant.Conclusions:?Socio-economic differences are greater in a large urban city (Krakow), and affect variation in age at menarche. However, within smaller populations (Opole, Nowy Sacz) living in towns and villages, the difference in age at menarche is less visible. In addition, variation between areas reveals a lower age at menarche in urban as compared with non-urban areas.Résumé. Arrière plan: L’âge aux premières règles est une mesure importante de la maturation sexuelle des filles ainsi qu’un indicateur sensible des conditions du milieu au cours de l’enfance.Objectif: Cette étude analyse l’association entre âge aux premières règles et facteurs socio-économiques (urbanisation, taille de la population, éducation parentale et nombre d’enfants dans la famille).Sujets et méthodes: Des données par questionnaire ont été rassemblées sur 3271 écoliers habitant dans trois provinces du sud de la Pologne, nés entre 1981 et 1984. L’âge aux premières règles a été estimé par la méthode de mémorisation. Des analyses de régression multiple et de covariance (ANCOVA) ont été effectuées afin d’évaluer la signification statistique des différences entre groupes.Résultats: Les filles de familles à statut socio-économique élevé sont plus précoces que celles de statut socio-économique défavorable, mais suivant la région et la dimension de la population, d’autres facteurs influencent l’âge aux premières règles. Dans la province de Cracovie, l’urbanisation, l’éducation du père et le nombre d’enfants dans la famille jouent un rôle significatif. Dans la province d’Opole, ce sont l’urbanisation, l’éducation du père et le nombre d’enfants dans la famille qui interviennent, alors que dans la province de Nowi Sacz, est significatif le nombre d’enfants dans la famille.Conclusions: Les différences socio-économiques sont plus significatives dans une grande ville (Cracovie), alors que dans les ensembles populationnels plus restreints (Opole, Nowy Sacz), elles sont de moindre importance. Par ailleurs, la variation entre régions révèle un âge aux premières règles plus précoce chez les filles urbaines que chez les rurales.Zusammenfassung. Hintergrund: Das Menarchealter ist das wichtigste Maß für die sexuelle Reife bei Mädchen und ein empfindlicher Indikator für Umweltbedingungen während der Kindheit.Ziel: Die Studie analysierte die Beziehung zwischen Menarchealter und sozio-ökonomischen Kennzeichen (Urbanisation, Populationsgröße, Schulbildung der Eltern und Anzahl der Kinder pro Familie).Probanden und Methoden: Mittels Fragebögen wurden Daten von 3271 Schülerinnen, geboren zwischen 1981 und 1984, aus drei Provinzen Südpolens erhoben. Das Menarchealter wurde retrospektiv erfragt und basiert auf Angaben zur Menarche von den Studienteilnehmerinnen. Es wurden ANCOVA und multiple Regressionsanalysen verwendet, um Unterschiede zwischen den Gruppen auf statistische Signifikanz zu testen.Ergebnisse: Mädchen aus Familien der oberen sozio-ökonomischen Schicht menstruieren früher als Mädchen aus Familien niederer sozio-ökonomischer Schichten. Je nach geographischer Region und Populationsgröße gibt es jedoch noch weitere Faktoren, die das Menarchealter beeinflussten. Faktoren, die in der Provinz Krakau signifikanten Einfluss auf das Menarchealter zeigen, sind Urbanisationsgrad, Schulbildung des Vaters und Anzahl der Kinder in der Familie; in der Provinz Oppeln beinhalten diese Faktoren den Urbanisationsgrad und die Anzahl der Kinder in der Familie, während in der Provinz Novy Sacz nur die Anzahl der Kinder in der Familie Signifikanzniveau erreichen.Zusammenfassung: Sozio-ökonomische Unterschiede sind in einer Großstadt (Krakau) größer und nehmen Einfluss auf die Variation des Menarchealters. In den weniger umfangreichen Populationen (Oppeln, Novy Sacz) aus kleineren Städten und Dörfern ist dagegen der Unterschied im Menarchealter weniger offensichtlich. Darüber hinaus zeigt die Variation zwischen Regionen, dass das Menarchealter in städtischen Gegenden niedriger ist als in ländlichen.Resumen. Antecedentes: La edad de menarquia es la medida más importante de la maduración sexual en chicas y un sensible indicador de las condiciones ambientales durante la infancia.Objetivo: El estudio analizó la asociación entre la edad de menarquia y características socioeconómicas (urbanización, tamaño poblacional, educación de los padres y número de hijos en la familia).Sujetos y métodos: Los datos del cuestionario se recogieron en 3271 niñas escolares nacidas entre 1981 y 1984, que residían en tres provincias del sur de Polonia. La edad de menarquia se estimó por el método retrospectivo y se basó en la fecha de menarquia proporcionada por las participantes en el estudio. Se aplicaron los análisis ANCOVA y de regresión múltiple para comprobar la significación estadística de las diferencias entre grupos.Resultados: Las chicas de familias con un nivel socioeconómico elevado experimentan la menarquia a una edad más temprana que las de familias con un nivel socioeconómico bajo. Sin embargo, dependiendo de la región geográfica y del tamaño poblacional, existen otros factores que influyen sobre la edad de menarquia. En la provincia de Cracovia, los factores que producen diferencias significativas en la edad de menarquia son la urbanización, la educación del padre y el número de hijos en la familia; en la provincia de Opole, estos factores incluyen la urbanización y el número de hijos de la familia, mientras que en la provincia de Nowy Sacz, es significativo el número de hijos por familia.Conclusiones: Las diferencias socioeconómicas son mayores en una gran urbe (Cracovia) y afectan a la variación en la edad de menarquia. Sin embargo, dentro de poblaciones más pequeñas (Opole, Nowy Sacz), viviendo en pueblos y aldeas, la diferencia en la edad de menarquia es menos evidente. Además, la variación entre áreas revela una menor edad de menarquia en el medio urbano comparado con las áreas no urbanas. 相似文献