全文获取类型
收费全文 | 4886篇 |
免费 | 334篇 |
国内免费 | 31篇 |
专业分类
耳鼻咽喉 | 24篇 |
儿科学 | 131篇 |
妇产科学 | 90篇 |
基础医学 | 765篇 |
口腔科学 | 137篇 |
临床医学 | 462篇 |
内科学 | 1046篇 |
皮肤病学 | 107篇 |
神经病学 | 606篇 |
特种医学 | 139篇 |
外科学 | 444篇 |
综合类 | 21篇 |
预防医学 | 454篇 |
眼科学 | 67篇 |
药学 | 371篇 |
中国医学 | 6篇 |
肿瘤学 | 381篇 |
出版年
2024年 | 16篇 |
2023年 | 78篇 |
2022年 | 132篇 |
2021年 | 247篇 |
2020年 | 167篇 |
2019年 | 181篇 |
2018年 | 226篇 |
2017年 | 143篇 |
2016年 | 171篇 |
2015年 | 210篇 |
2014年 | 260篇 |
2013年 | 320篇 |
2012年 | 466篇 |
2011年 | 439篇 |
2010年 | 241篇 |
2009年 | 184篇 |
2008年 | 293篇 |
2007年 | 325篇 |
2006年 | 253篇 |
2005年 | 247篇 |
2004年 | 221篇 |
2003年 | 154篇 |
2002年 | 136篇 |
2001年 | 18篇 |
2000年 | 7篇 |
1999年 | 23篇 |
1998年 | 18篇 |
1997年 | 21篇 |
1996年 | 12篇 |
1995年 | 7篇 |
1994年 | 15篇 |
1993年 | 6篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1986年 | 1篇 |
1983年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有5251条查询结果,搜索用时 15 毫秒
71.
Selina Dürr David Miedinger Esther Helen Steveling Sabrina Maier Jörg Daniel Leuppi 《COPD》2014,11(6):689-696
Introduction: In the therapy of chronic obstructive pulmonary disease (COPD), it is a major goal to improve health-related quality of life (HRQOL). Patients with COPD often suffer from exertional dyspnea and adopt a sedentary lifestyle, which could be associated with poorer HRQOL. The aim of this study was to investigate the independent association of objectively measured daily physical activity and functional capacity with HRQOL in patients with COPD. Methods: In this cross-sectional study conducted at the University Hospital Basel, Switzerland, 87 stable patients (58.6% male, mean age: 67.3 ± 9.6 yrs) with COPD in GOLD grades I (n = 23), II (n = 46), III (n = 12) and IV (n = 6) were investigated. To assess HRQOL, the COPD assessment test (CAT) was completed. Patients performed spirometry and 6-min walk test. Physical activity was measured by the SenseWear Mini Armband on 7 consecutive days. By performing a multiple linear regression analysis, independent predictors of CAT score were identified. Results: Age (β = ?0.39, p = 0.001), average daily steps (β = ?0.31, p = 0.033) and 6-min walk distance (β = ?0.32, p = 0.019) were found to be independent predictors of CAT score, whereas physical activity duration above 3 METs (p = 0.498) and forced expiratory volume in 1 s in% of predicted (p = 0.364) showed no significant association. Conclusions: This study showed that average daily steps and functional capacity are independent determinants of HRQOL in patients with COPD. This emphasizes the importance to remain active and mobile, which is associated with better HRQOL. 相似文献
72.
73.
74.
Sabrina Trapp Karsten Mueller Jöran Lepsien Bernd Krämer Oliver Gruber 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2014,232(2):619-628
Many studies have demonstrated attenuated verbal working memory (WM) under articulatory suppression. However, performance is not completely abolished, suggesting a less efficient, non-articulatory mechanism for the maintenance of verbal information. The neural causes for the reduced efficiency of such a putative complementary maintenance system have not yet been addressed. The present study was conducted to fill this gap. Subjects performed a Sternberg task (a) under articulatory maintenance at low, high, and supracapacity set sizes and (b) under non-articulatory maintenance at low and high set sizes. With functional magnetic resonance imaging, set-size related increases in activity were compared between subvocal articulatory rehearsal and non-articulatory maintenance. First, the results replicate previous findings showing different networks underlying these two maintenance strategies. Second, activation of all key nodes of the articulatory maintenance network increased with the amount of memorized information, showing no plateau at high set sizes. In contrast, for non-articulatory maintenance, there was evidence for a plateau at high set sizes in all relevant areas of the network. Third, for articulatory maintenance, the non-articulatory maintenance network was additionally recruited at supracapacity set sizes, presumably to assist processing in this highly demanding condition. This is the first demonstration of differential neural bottlenecks for articulatory and non-articulatory maintenance. This study adds to our understanding of the performance differences between these two strategies supporting verbal WM. 相似文献
75.
Karin Vogel Sabrina Thomann Benjamin Vogel Philipp Schuster Barbara Schmidt 《Immunology》2014,143(4):588-600
Herpes simplex virus type 1 (HSV‐1), a member of the herpes virus family, is characterized by a short replication cycle, high cytopathogenicity and distinct neurotropism. Primary infection and reactivation may cause severe diseases in immunocompetent and immunosuppressed individuals. This study investigated the role of human plasmacytoid dendritic cells (pDC) in the activation of natural killer (NK) cells for the control of herpesviral infections. Within peripheral blood mononuclear cells, UV‐inactivated HSV‐1 and CpG‐A induced CD69 up‐regulation on NK cells, whereas infectious HSV‐1 was particularly active in inducing NK cell effector functions interferon‐γ (IFN‐γ) secretion and degranulation. The pDC‐derived IFN‐α significantly contributed to NK cell activation, as evident from neutralization and cell depletion experiments. In addition, monocyte‐derived tumour necrosis factor‐α (TNF‐α) induced after exposure to infectious HSV‐1 was found to stimulate IFN‐γ secretion. A minority of monocytes was shown to be non‐productively infected in experiments using fluorescently labelled viruses and quantitative PCR analyses. HSV‐1‐exposed monocytes up‐regulated classical HLA‐ABC and non‐classical HLA‐E molecules at the cell surface in an IFN‐α‐dependent manner, whereas stress molecules MICA/B were not induced. Notably, depletion of monocytes reduced NK cell effector functions induced by infectious HSV‐1 (P < 0·05). Altogether, our data suggest a model in which HSV‐1‐stimulated pDC and monocytes activate NK cells via secretion of IFN‐α and TNF‐α. In addition, infection of monocytes induces NK cell effector functions via TNF‐α‐dependent and TNF‐α‐independent mechanisms. Hence, pDC and monocytes, which are among the first cells infiltrating herpetic lesions, appear to have important bystander functions for NK cells to control these viral infections. 相似文献
76.
Alexandre Kanashiro Thais Oliveira de Lucena Leoncio Ayda Henriques Schneider Hélio Rocha Alves Gabriel Shimizu Bassi Sabrina Graziani Veloso Dutra Fernando de Queiróz Cunha Luis Ulloa David do Carmo Malvar 《Pharmacological reports : PR》2019,71(6):1095-1103
BackgroundThe regulation of the immune system by the sympathetic nervous system is allowing the design of novel treatments for inflammatory disorders such as arthritis. In this study, we have analyzed the effects of α- and β-adrenoceptor agonists injected subcutaneously, intrathecally, or intra-articularly in zymosan-induced arthritis.MethodsMurine arthritis was induced by intra-articular (knee joint) injection of zymosan. α1 (phenylephrine), α2 (clonidine), β1 (dobutamine), or β2 (salbutamol)-adrenoceptor agonists were injected subcutaneously (sc), intrathecally (it), or intra-articularly (ia) to activate peripheral, spinal, or intra-articular adrenoceptors and to study their effects on articular edema formation and neutrophil migration into the synovial cavity.ResultsTreatments with phenylephrine did not affect the edema formation, but it increased neutrophil migration when injected subcutaneously (155.3%) or intra-articularly (187.7%). Treatments with clonidine inhibited neutrophil migration (59.9% sc, 68.7% it, 42.8% ia) regardless of the route of administration, but it inhibited edema formation only when injected intrathecally (66.7%) or intra-articularly (36%) but not subcutaneously. Treatments with dobutamine inhibited both edema (42.0% sc, 69.5% it, 61.6% ia) and neutrophil migration (28.4% sc, 70.3% it, 82.4% ia) in a concentration dependent manner. Likewise, all the treatments with salbutamol also inhibited edema formation (89.9% sc, 62.4% it, 69.8% ia) and neutrophil migration (76.6% sc, 39.1% it, 71.7% ia).ConclusionWhereas the β-adrenoceptor agonists induced anti-inflammatory effects regardless of their route of administration, α1- and α2-adrenoceptor agonists induced either pro- and anti-inflammatory effects, respectively. 相似文献
77.
Work Productivity Loss in Early Arthritis During the First 3 Years of Disease: A Study From a French National Multicenter Cohort 下载免费PDF全文
78.
Andrea Franceschini Roger Meier Alain Casanova Saskia Kreibich Neha Daga Daniel Andritschke Sabrina Dilling Pauli R?m? Mario Emmenlauer Andreas Kaufmann Raquel Conde-álvarez Shyan Huey Low Lucas Pelkmans Ari Helenius Wolf-Dietrich Hardt Christoph Dehio Christian von Mering 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(12):4548-4553
79.
Martin Kaltenpoth Kerstin Roeser-Mueller Sabrina Koehler Ashley Peterson Taras Y. Nechitaylo J. William Stubblefield Gudrun Herzner Jon Seger Erhard Strohm 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(17):6359-6364
Many insects rely on symbiotic microbes for survival, growth, or reproduction. Over evolutionary timescales, the association with intracellular symbionts is stabilized by partner fidelity through strictly vertical symbiont transmission, resulting in congruent host and symbiont phylogenies. However, little is known about how symbioses with extracellular symbionts, representing the majority of insect-associated microorganisms, evolve and remain stable despite opportunities for horizontal exchange and de novo acquisition of symbionts from the environment. Here we demonstrate that host control over symbiont transmission (partner choice) reinforces partner fidelity between solitary wasps and antibiotic-producing bacteria and thereby stabilizes this Cretaceous-age defensive mutualism. Phylogenetic analyses show that three genera of beewolf wasps (Philanthus, Trachypus, and Philanthinus) cultivate a distinct clade of Streptomyces bacteria for protection against pathogenic fungi. The symbionts were acquired from a soil-dwelling ancestor at least 68 million years ago, and vertical transmission via the brood cell and the cocoon surface resulted in host–symbiont codiversification. However, the external mode of transmission also provides opportunities for horizontal transfer, and beewolf species have indeed exchanged symbiont strains, possibly through predation or nest reuse. Experimental infection with nonnative bacteria reveals that—despite successful colonization of the antennal gland reservoirs—transmission to the cocoon is selectively blocked. Thus, partner choice can play an important role even in predominantly vertically transmitted symbioses by stabilizing the cooperative association over evolutionary timescales.Cooperation is ubiquitous in nature, yet it presents a conundrum to evolutionary biology because acts that are beneficial to the receiver but costly to the actor should not be favored by natural selection (1). In interspecific associations (i.e., symbioses), the two most important models to explain the maintenance of cooperation are partner fidelity and partner choice (2, 3). In partner-fidelity associations, host and symbiont interact repeatedly and reward cooperating individuals while punishing cheaters, thereby reinforcing mutually beneficial interactions (2, 4). In partner-choice associations, individuals may interact only once, but one member can select its partner in advance of any possible exploitation (2, 4). Partner choice appears to select for cooperative strains among environmentally acquired microbial symbionts, e.g., the bioluminescent Vibrio fischeri bacteria of squids (5), the nitrogen-fixing rhizobia of legumes (6), and mycorrhizal fungi of plants (7). By contrast, partner fidelity is generally assumed to be the major stabilizing force in the widespread and ecologically important vertically transmitted symbioses of insects (4).However, localization and transmission routes of mutualistic bacteria in insects are diverse, and the differences across symbiotic systems have important implications for the evolutionary trajectory of the associations. Symbionts with an obligate intracellular lifestyle are usually tightly integrated into the host’s metabolism (e.g., ref. 8) and development (9), and the mutual interdependence of both partners coincides with perfect vertical symbiont transmission. Over evolutionary timescales, the high degree of partner fidelity results in host–symbiont cocladogenesis, and, concordantly, phylogenies of hosts and their intracellular symbionts are often found to be congruent (10–13). Although such a pattern is also observed for some extracellular symbioses with especially tight host–symbiont integration (14, 15), the ability of many extracellularly transmitted symbionts to spend part of their life cycle outside of the host’s body is often reflected in more or less extensive horizontal transmission or de novo acquisition of symbionts from the environment (16, 17). In these cases, partner choice mechanisms are expected to ensure specificity in the establishment and maintenance of the association (18). The nature of such control mechanisms, however, remains poorly understood.Although many of the well-studied mutualistic associations in insects have a nutritional basis (19, 20), an increasing number of symbioses for the defense of the host against predators (21), parasitoids (22), or pathogens (23–25) have recently been discovered. Among defensive symbionts, Actinobacteria are particularly prevalent, probably due to their ubiquity in the soil and their ability to produce secondary metabolites with antibiotic properties (23). Antibiotic-producing actinobacterial symbionts have been discovered on the cuticle of leaf-cutting ants (26), in the fungal galleries of a bark beetle (27), and in the antennae and on cocoons of beewolf wasps (28). While in the former two cases the symbionts have been implicated in the defense of the hosts’ nutritional resources against competing fungi (26, 27), the beewolves’ bacteria protect the offspring in the cocoon against pathogenic microorganisms (28, 29).Beewolves are solitary wasps in the genera Philanthus, Trachypus, and Philanthinus (Hymenoptera, Crabronidae, Philanthini). They engage in a defensive alliance with the Actinobacterium ‘Candidatus Streptomyces philanthi’ (CaSP) (28, 30, 31), which is cultivated by female beewolves in specialized antennal gland reservoirs (32). The uniqueness and complexity of the glands suggest a long history of host adaptation towards cultivating its actinobacterial symbionts (32). From the antennae, the streptomycetes are secreted into the brood cell, taken up by the larva, and incorporated into its cocoon (33), where they provide protection against pathogenic fungi and bacteria (28) by producing at least nine different antimicrobial compounds (29). Weeks or months later, eclosing adult females acquire the bacteria from the cocoon surface (33), thus completing the vertical transmission of CaSP. However, this mode of transmission provides opportunities for the horizontal transfer of symbionts among beewolf species or the de novo uptake of bacteria from the environment. Despite these opportunities, a monophyletic clade of CaSP strains has previously been found in 31 species of beewolves, suggesting an ancient and highly coevolved relationship (30, 31, 34).Here we combine cophylogenetic analyses of beewolves and their vertically transmitted defensive symbionts with experimental manipulation of symbiont infection status and subsequent observations of transmission from female antennal gland reservoirs into the brood cell to (i) reconstruct the coevolutionary history of the symbiosis, (ii) estimate the age of the symbiosis, (iii) elucidate the ancestral lifestyle of the symbionts, and (iv) assess the importance of partner fidelity and partner choice for the long-term stability of the association. 相似文献