全文获取类型
收费全文 | 4435篇 |
免费 | 421篇 |
国内免费 | 68篇 |
专业分类
耳鼻咽喉 | 14篇 |
儿科学 | 44篇 |
妇产科学 | 49篇 |
基础医学 | 639篇 |
口腔科学 | 47篇 |
临床医学 | 414篇 |
内科学 | 321篇 |
皮肤病学 | 10篇 |
神经病学 | 2028篇 |
特种医学 | 161篇 |
外科学 | 236篇 |
综合类 | 209篇 |
预防医学 | 131篇 |
眼科学 | 76篇 |
药学 | 357篇 |
中国医学 | 46篇 |
肿瘤学 | 142篇 |
出版年
2024年 | 19篇 |
2023年 | 249篇 |
2022年 | 373篇 |
2021年 | 422篇 |
2020年 | 350篇 |
2019年 | 196篇 |
2018年 | 226篇 |
2017年 | 285篇 |
2016年 | 280篇 |
2015年 | 333篇 |
2014年 | 377篇 |
2013年 | 244篇 |
2012年 | 219篇 |
2011年 | 141篇 |
2010年 | 244篇 |
2009年 | 214篇 |
2008年 | 74篇 |
2007年 | 75篇 |
2006年 | 48篇 |
2005年 | 33篇 |
2004年 | 24篇 |
2003年 | 28篇 |
2002年 | 40篇 |
2001年 | 39篇 |
2000年 | 28篇 |
1999年 | 60篇 |
1998年 | 51篇 |
1997年 | 38篇 |
1996年 | 58篇 |
1995年 | 44篇 |
1994年 | 27篇 |
1993年 | 18篇 |
1992年 | 18篇 |
1991年 | 18篇 |
1990年 | 13篇 |
1989年 | 13篇 |
1988年 | 5篇 |
排序方式: 共有4924条查询结果,搜索用时 812 毫秒
1.
《Health & place》2022
PurposeAccording to the social determinants of health framework, income inequality is a potential risk factor for adverse mental health. However, few studies have explored the mechanisms suspected to mediate this relationship. The current study addresses this gap through a mediation analysis to determine if social support and community engagement act as mediators linking neighbourhood income inequality to maternal anxiety and depressive symptoms within a cohort of new mothers living in the City of Calgary, Canada.MethodsData collected at three years postpartum from mothers belonging to the All Our Families (AOF) cohort were used in the current study. Maternal data were collected between 2012 and 2015 and linked to neighbourhood socioeconomic data from the 2006 Canadian Census. Income inequality was measured using Gini coefficients derived from 2006 after-tax census data. Generalized structural equation models were used to quantify the associations between income inequality and mental health symptoms, and to assess the potential direct and indirect mediating effects of maternal social support and community engagement.ResultsIncome inequality was not significantly associated with higher depressive symptoms (β = 0.32, 95%CI = −0.067, 0.70), anxiety symptoms (β = 0.11, 95%CI = −0.39, 0.60), or lower social support. Income inequality was not associated with community engagement. For the depression models, higher social support was significantly associated with lower depressive symptoms (β = −0.13, 95%CI = −0.15, −0.097), while community engagement was not significantly associated with depressive symptoms (β = 0.059, 95%CI = −0.15, 0.27). Similarly, for the anxiety models, lower anxiety symptoms were significantly associated with higher levels of social support (β = −0.17, 95%CI = −0.20, −0.13) but not with higher levels of community engagement (β = 0.14, 95%CI = −0.14, 0.41).ConclusionThe current study did not find clear evidence for social support or community engagement mediating the relationship between neighbourhood income inequality and maternal mental health. Future investigations should employ a broader longitudinal approach to capture changes in income inequality, potential mediators, and mental health symptomatology over time. 相似文献
2.
Investigation of image reconstruction from data collected over a limited-angular range in X-ray CT remains a topic of active research because it may yield insight into the development of imaging workflow of practical significance. This reconstruction problem is well-known to be challenging, however, because it is highly ill-conditioned. In the work, we investigate optimization-based image reconstruction from data acquired over a limited-angular range that is considerably smaller than the angular range in short-scan CT. We first formulate the reconstruction problem as a convex optimization program with directional total-variation (TV) constraints applied to the image, and then develop an iterative algorithm, referred to as the directional-TV (DTV) algorithm for image reconstruction through solving the optimization program. We use the DTV algorithm to reconstruct images from data collected over a variety of limited-angular ranges for breast and bar phantoms of clinical- and industrial-application relevance. The study demonstrates that the DTV algorithm accurately recovers the phantoms from data generated over a significantly reduced angular range, and that it considerably diminishes artifacts observed otherwise in reconstructions of existing algorithms. We have also obtained empirical conditions on minimal-angular ranges sufficient for numerically accurate image reconstruction with the DTV algorithm. 相似文献
3.
Huang Liyan Li Wei Li Yi Song Chaoyuan Wang Pin Wang Hongchun Sun Xiulian 《Neurogenetics》2020,21(1):39-49
neurogenetics - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic disease leading to stroke and vascular dementia.... 相似文献
4.
Y.R. Song B. Wu Y.T. Yang J. Chen L.J. Zhang Z.W. Zhang H.Y. Shi C.L. Huang J.X. Pan P. Xie 《Brazilian journal of medical and biological research》2015,48(11):973-982
Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2%
of the general population of different European countries. Unfortunately, there is no
objective laboratory-based test to aid BD diagnosis or monitor its progression, and
little is known about the molecular basis of BD. Here, we performed a comparative
proteomic study to identify differentially expressed plasma proteins in various BD
mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A
total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched
healthy control subjects were recruited. Seven high-abundance proteins were
immunodepleted in plasma samples from the 4 experimental groups, which were then
subjected to proteome-wide expression profiling by two-dimensional electrophoresis
and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem
mass spectrometry. Proteomic results were validated by immunoblotting and
bioinformatically analyzed using MetaCore. From a total of 32 proteins identified
with 1.5-fold changes in expression compared with healthy controls, 16 proteins were
perturbed in BD independent of mood state, while 16 proteins were specifically
associated with particular BD mood states. Two mood-independent differential
proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be
associated with early perturbations in lipid metabolism. Moreover, down-regulation of
one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved
in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be
associated with early perturbations in lipid metabolism that are independent of mood
state, while CA-1 may be involved in the pathophysiology of depressive episodes. 相似文献
5.
6.
Xue Wen Ping An Hexuan Li Zijian Zhou Yimin Sun Jian Wang Lixiang Ma Boxun Lu 《神经科学通报》2020,36(12):1414
Expansions of trinucleotide or hexanucleotide repeats lead to several neurodegenerative disorders, including Huntington disease [caused by expanded CAG repeats (CAGr) in the HTT gene], and amyotrophic lateral sclerosis [ALS, possibly caused by expanded GGGGCC repeats (G4C2r) in the C9ORF72 gene], of which the molecular mechanisms remain unclear. Here, we demonstrated that lowering the Drosophila homologue of tau protein (dtau) significantly rescued in vivo neurodegeneration, motor performance impairments, and the shortened life-span in Drosophila expressing expanded CAGr or expanded G4C2r. Expression of human tau (htau4R) restored the disease-related phenotypes that had been mitigated by the loss of dtau, suggesting an evolutionarily-conserved role of tau in neurodegeneration. We further revealed that G4C2r expression increased tau accumulation by inhibiting autophagosome–lysosome fusion, possibly due to lowering the level of BAG3, a regulator of autophagy and tau. Taken together, our results reveal a novel mechanism by which expanded G4C2r causes neurodegeneration via an evolutionarily-conserved mechanism. Our findings provide novel autophagy-related mechanistic insights into C9ORF72-ALS and possible entry points to disease treatment.Electronic supplementary materialThe online version of this article (10.1007/s12264-020-00518-2) contains supplementary material, which is available to authorized users. 相似文献
7.
《Biomaterials》2015
Podophyllotoxin (PPT) exhibited significant activity against P-glycoprotein mediated multidrug resistant (MDR) tumor cell lines; however, due to its poor solubility and high toxicity, PPT cannot be dosed systemically, preventing its clinical use for MDR cancer. We developed a nanoparticle dosage form of PPT by covalently conjugating PPT and polyethylene glycol (PEG) with acetylated carboxymethyl cellulose (CMC-Ac) using one-pot esterification chemistry. The polymer conjugates self-assembled into nanoparticles (NPs) of variable sizes (20–120 nm) depending on the PPT-to-PEG molar ratio (2–20). The conjugate with a low PPT/PEG molar ratio of 2 yielded NPs with a mean diameter of 20 nm and released PPT at ∼5%/day in serum, while conjugates with increased PPT/PEG ratios (5 and 20) produced bigger particles (30 nm and 120 nm respectively) that displayed slower drug release (∼2.5%/day and ∼1%/day respectively). The 20 nm particles exhibited 2- to 5-fold enhanced cell killing potency and 5- to 20-fold increased tumor delivery compared to the larger NPs. The biodistribution of the 20 nm PPT-NPs was highly selective to the tumor with 8-fold higher accumulation than all other examined tissues, while the larger PPT-NPs (30 and 120 nm) exhibited increased liver uptake. Within the tumor, >90% of the 20 nm PPT-NPs penetrated to the hypovascular core, while the larger particles were largely restricted in the hypervascular periphery. The 20 nm PPT-NPs displayed significantly improved efficacy against MDR tumors in mice compared to the larger PPT-NPs, native PPT and the standard taxane chemotherapies, with minimal toxicity. 相似文献
8.
《Neuropsychopharmacology》2019,85(11):956-965
BackgroundBinge eating and other forms of disordered eating behavior (DEB) are associated with failed inhibitory control. This study investigated the neural correlates of failed inhibitory control as a potential biomarker for DEB.MethodsThe study used prospective longitudinal data from the European IMAGEN study adolescent cohort. Participants completed baseline assessments (questionnaires and a brain scan [functional magnetic resonance imaging]) at 14 years of age and a follow-up assessment (questionnaires) at 16 years of age. Self-reported binge eating and/or purging were used to indicate presence of DEB. Neural correlates of failed inhibition were assessed using the stop signal task. Participants were categorized as healthy control subjects (reported no DEB at both time points), maintainers (reported DEB at both time points), recoverers (reported DEB at baseline only), and developers (reported DEB at follow-up only). Forty-three individuals per group with complete scanning data were matched on gender, age, puberty, and intelligence (N = 172).ResultsAt baseline, despite similar task performance, incorrectly responding to stop signals (failed inhibitory control) was associated with greater recruitment of the medial prefrontal cortex and anterior cingulate cortex in the developers compared with healthy control subjects and recoverers.ConclusionsGreater recruitment of the medial prefrontal and anterior cingulate regions during failed inhibition accords with abnormal evaluation of errors contributing to DEB development. As this precedes symptom onset and is evident despite normal task performance, neural responses during failed inhibition may be a useful biomarker of vulnerability for DEB. This study highlights the potential value of prospective neuroimaging studies for identifying markers of illness before the emergence of behavior changes. 相似文献
9.
10.
When living organisms become sick as a result of a bacterial infection, a suite of brain-mediated responses occur, including fever, anorexia and sleepiness. Systemic administration of lipopolysaccharide (LPS), a common constituent of bacterial cell walls, increases body temperature and non-rapid eye movement (NREM) sleep in animals and induces the production of pro-inflammatory prostaglandins (PGs). PGE2 is the principal mediator of fever, and both PGE2 and PGD2 regulate sleep–wake behavior. The extent to which PGE2 and PGD2 are involved in the effect of LPS on NREM sleep remains to be clarified. Therefore, we examined LPS-induced changes in body temperature and NREM sleep in mice with nervous system-specific knockouts (KO) for the PGE2 receptors type EP3 or EP4, in mice with total body KO of microsomal PGE synthase-1 or the PGD2 receptor type DP, and in mice treated with the cyclooxygenase (COX) inhibitor meloxicam. We observed that LPS-induced NREM sleep was slightly attenuated in mice lacking EP4 receptors in the nervous system, but was not affected in any of the other KO mice or in mice pretreated with the COX inhibitor. These results suggest that the effect of LPS on NREM sleep is partially dependent on PGs and is likely mediated mainly by other pro-inflammatory substances. In addition, our data show that the main effect of LPS on body temperature is hypothermia in the absence of nervous system EP3 receptors or in the presence of a COX inhibitor. 相似文献