全文获取类型
收费全文 | 1348篇 |
免费 | 88篇 |
国内免费 | 1篇 |
出版年
2023年 | 10篇 |
2022年 | 4篇 |
2021年 | 32篇 |
2020年 | 24篇 |
2019年 | 18篇 |
2018年 | 33篇 |
2017年 | 26篇 |
2016年 | 37篇 |
2015年 | 70篇 |
2014年 | 82篇 |
2013年 | 92篇 |
2012年 | 134篇 |
2011年 | 142篇 |
2010年 | 65篇 |
2009年 | 62篇 |
2008年 | 68篇 |
2007年 | 88篇 |
2006年 | 54篇 |
2005年 | 72篇 |
2004年 | 50篇 |
2003年 | 39篇 |
2002年 | 56篇 |
2001年 | 12篇 |
2000年 | 10篇 |
1999年 | 16篇 |
1998年 | 11篇 |
1997年 | 7篇 |
1996年 | 9篇 |
1995年 | 15篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 12篇 |
1991年 | 4篇 |
1990年 | 7篇 |
1989年 | 12篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1986年 | 6篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 5篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1970年 | 4篇 |
1969年 | 3篇 |
1968年 | 3篇 |
1962年 | 2篇 |
1952年 | 1篇 |
排序方式: 共有1437条查询结果,搜索用时 31 毫秒
71.
Background
As primary healthcare professionals, community pharmacists have both opportunity and potential to contribute to the prevention and progression of chronic diseases. Using cardiovascular disease (CVD) as a case study, we explored factors that influence community pharmacists’ everyday practice in this area. We also propose a model to best illustrate relationships between influencing factors and the scope of community pharmacy practice in the care of clients with established CVD.Methods
In-depth, semi-structured interviews were conducted with 21 community pharmacists in New South Wales, Australia. All interviews were audio-recorded, transcribed ad verbatim, and analysed using a “grounded-theory” approach.Results
Our model shows that community pharmacists work within a complex system and their practice is influenced by interactions between three main domains: the “people” factors, including their own attitudes and beliefs as well as those of clients and doctors; the “environment” within and beyond the control of community pharmacy; and outcomes of their professional care. Despite the complexity of factors and interactions, our findings shed some light on the interrelationships between these various influences. The overarching obstacle to maximizing the community pharmacists’ contribution is the lack of integration within health systems. However, achieving better integration of community pharmacists in primary care is a challenge since the systems of remuneration for healthcare professional services do not currently support this integration.Conclusion
Tackling chronic diseases such as CVD requires mobilization of all sources of support in the community through innovative policies which facilitate inter-professional collaboration and team care to achieve the best possible healthcare outcomes for society. 相似文献72.
Birgitte Nygaard Niels Erik Frandsen Lisbet Brandi Knud Rasmussen Ove Vyff Oestergaard Lars Oedum Hans Christian Hoeck Ditte Hansen 《PloS one》2014,9(8)
Background
Vitamin D repletion with high doses of vitamin D is often recommended to patients and healthy subjects. The safety, especially concerning changes in urinary calcium excretion is of great importance.Methods
In a double-blinded, placebo-controlled study in 40 healthy volunteers, we examined the changes in mineral metabolism during supplementation with 3000 IU of oral cholecalciferol daily during 4 months.Results
Both 25(OH)vitamin D and 1,25(OH)2vitamin D increased significantly in the active treated group as compared to the placebo group (186% versus 14% (P<0.001) and 28% versus – 8% (P<0.001)). No change was observed in urinary calcium excretion in the active group compared to the placebo group (P = 0.891). Fibroblast growth factor 23 increased significantly by 10% (P<0.018) in the active group. However, there was no difference in changes in FGF23 between treatment groups (P = 0.457).Conclusion
High dose cholecalciferol significantly increases 25(OH)vitamin D and 1,25(OH)2vitamin D levels compared to placebo. No changes in urinary calcium excretion or other measured components of the mineral metabolism were found between groups.Trial Registration
ClinicalTrials.gov . NCT00952562相似文献73.
Robert C. Speth Eduardo J. Carrera Catalina Bretón Andrea Linares Luz Gonzalez-Reiley Jamala D. Swindle Kira L. Santos Ines Schadock Michael Bader Vardan T. Karamyan 《PloS one》2014,9(8)
The recent identification of a novel binding site for angiotensin (Ang) II as the peptidase neurolysin (E.C. 3.4.24.16) has implications for the renin-angiotensin system (RAS). This report describes the distribution of specific binding of 125I-Sarcosine1, Isoleucine8 Ang II (125I-SI Ang II) in neurolysin knockout mouse brains compared to wild-type mouse brains using quantitative receptor autoradiography. In the presence of p-chloromercuribenzoic acid (PCMB), which unmasks the novel binding site, widespread distribution of specific (3 µM Ang II displaceable) 125I-SI Ang II binding in 32 mouse brain regions was observed. Highest levels of binding >700 fmol/g initial wet weight were seen in hypothalamic, thalamic and septal regions, while the lowest level of binding <300 fmol/g initial wet weight was in the mediolateral medulla. 125I-SI Ang II binding was substantially higher by an average of 85% in wild-type mouse brains compared to neurolysin knockout brains, suggesting the presence of an additional non-AT1, non-AT2, non-neurolysin Ang II binding site in the mouse brain. Binding of 125I-SI Ang II to neurolysin in the presence of PCMB was highest in hypothalamic and ventral cortical brain regions, but broadly distributed across all regions surveyed. Non-AT1, non-AT2, non-neurolysin binding was also highest in the hypothalamus but had a different distribution than neurolysin. There was a significant reduction in AT2 receptor binding in the neurolysin knockout brain and a trend towards decreased AT1 receptor binding. In the neurolysin knockout brains, the size of the lateral ventricles was increased by 56% and the size of the mid forebrain (−2.72 to +1.48 relative to Bregma) was increased by 12%. These results confirm the identity of neurolysin as a novel Ang II binding site, suggesting that neurolysin may play a significant role in opposing the pathophysiological actions of the brain RAS and influencing brain morphology. 相似文献
74.
Bone tissue engineering represents one of the most challenging emergent fields for scientists and clinicians.Current failures of autografts and allografts in many pathological conditions have prompted researchers to find new biomaterials able to promote bone repair or regeneration with specific characteristics of biocompatibility,biodegradability and osteoinductivity.Recent advancements for tissue regeneration in bone defects have occurred by following the diamond concept and combining the use of growth factors and mesenchymal stem cells(MSCs).In particular,a more abundant and easily accessible source of MSCs was recently discovered in adipose tissue.These adipose stem cells(ASCs)can be obtained in large quantities with little donor site morbidity or patient discomfort,in contrast to the invasive and painful isolation of bone marrow MSCs.The osteogenic potential of ASCs on scaffolds has been examined in cell cultures and animal models,with only a few cases reporting the use of ASCs for successful reconstruction or accelerated healing of defects of the skull and jaw in patients.Although these reports extend our limited knowledge concerning the use of ASCs for osseous tissue repair and regeneration,the lack of standardization in applied techniques makes the comparison between studies difficult.Additional clinical trials are needed to assess ASC therapy and address potential ethical and safety concerns,which must be resolved to permit application in regenerative medicine. 相似文献
75.
Bacteria,phages and pigs: the effects of in-feed antibiotics on the microbiome at different gut locations 总被引:1,自引:0,他引:1
Torey Looft Heather K Allen Brandi L Cantarel Uri Y Levine Darrell O Bayles David P Alt Bernard Henrissat Thaddeus B Stanton 《The ISME journal》2014,8(8):1566-1576
Disturbance of the beneficial gut microbial community is a potential collateral effect of antibiotics, which have many uses in animal agriculture (disease treatment or prevention and feed efficiency improvement). Understanding antibiotic effects on bacterial communities at different intestinal locations is essential to realize the full benefits and consequences of in-feed antibiotics. In this study, we defined the lumenal and mucosal bacterial communities from the small intestine (ileum) and large intestine (cecum and colon) plus feces, and characterized the effects of in-feed antibiotics (chlortetracycline, sulfamethazine and penicillin (ASP250)) on these communities. 16S rRNA gene sequence and metagenomic analyses of bacterial membership and functions revealed dramatic differences between small and large intestinal locations, including enrichment of Firmicutes and phage-encoding genes in the ileum. The large intestinal microbiota encoded numerous genes to degrade plant cell wall components, and these genes were lacking in the ileum. The mucosa-associated ileal microbiota harbored greater bacterial diversity than the lumen but similar membership to the mucosa of the large intestine, suggesting that most gut microbes can associate with the mucosa and might serve as an inoculum for the lumen. The collateral effects on the microbiota of antibiotic-fed animals caused divergence from that of control animals, with notable changes being increases in Escherichia coli populations in the ileum, Lachnobacterium spp. in all gut locations, and resistance genes to antibiotics not administered. Characterizing the differential metabolic capacities and response to perturbation at distinct intestinal locations will inform strategies to improve gut health and food safety. 相似文献
76.
Ines Teichert Eva Katharina Steffens Nicole Schna? Benjamin Fr?nzel Christoph Krisp Dirk A. Wolters Ulrich Kück 《PLoS genetics》2014,10(9)
Mitogen-activated protein kinase (MAPK) pathways are crucial signaling instruments in eukaryotes. Most ascomycetes possess three MAPK modules that are involved in key developmental processes like sexual propagation or pathogenesis. However, the regulation of these modules by adapters or scaffolds is largely unknown. Here, we studied the function of the cell wall integrity (CWI) MAPK module in the model fungus Sordaria macrospora. Using a forward genetic approach, we found that sterile mutant pro30 has a mutated mik1 gene that encodes the MAPK kinase kinase (MAPKKK) of the proposed CWI pathway. We generated single deletion mutants lacking MAPKKK MIK1, MAPK kinase (MAPKK) MEK1, or MAPK MAK1 and found them all to be sterile, cell fusion-deficient and highly impaired in vegetative growth and cell wall stress response. By searching for MEK1 interaction partners via tandem affinity purification and mass spectrometry, we identified previously characterized developmental protein PRO40 as a MEK1 interaction partner. Although fungal PRO40 homologs have been implicated in diverse developmental processes, their molecular function is currently unknown. Extensive affinity purification, mass spectrometry, and yeast two-hybrid experiments showed that PRO40 is able to bind MIK1, MEK1, and the upstream activator protein kinase C (PKC1). We further found that the PRO40 N-terminal disordered region and the central region encompassing a WW interaction domain are sufficient to govern interaction with MEK1. Most importantly, time- and stress-dependent phosphorylation studies showed that PRO40 is required for MAK1 activity. The sum of our results implies that PRO40 is a scaffold protein for the CWI pathway, linking the MAPK module to the upstream activator PKC1. Our data provide important insights into the mechanistic role of a protein that has been implicated in sexual and asexual development, cell fusion, symbiosis, and pathogenicity in different fungal systems. 相似文献
77.
Sonal Jaydeep Sidhaye Mandar Phatak Shamik Banerjee Aditya Mulay Ojas Deshpande Sourabh Bhide Tressa Jacob Ines Gehring Christiane Nuesslein-Volhard Mahendra Sonawane 《PLoS genetics》2014,10(9)
The epidermis is a stratified epithelium, which forms a barrier to maintain the internal milieu in metazoans. Being the outermost tissue, growth of the epidermis has to be strictly coordinated with the growth of the embryo. The key parameters that determine tissue growth are cell number and cell size. So far, it has remained unclear how the size of epidermal cells is maintained and whether it contributes towards epidermal homeostasis. We have used genetic analysis in combination with cellular imaging to show that zebrafish goosepimples/myosin Vb regulates plasma membrane homeostasis and is involved in maintenance of cell size in the periderm, the outermost epidermal layer. The decrease in peridermal cell size in Myosin Vb deficient embryos is compensated by an increase in cell number whereas decrease in cell number results in the expansion of peridermal cells, which requires myosin Vb (myoVb) function. Inhibition of cell proliferation as well as cell size expansion results in increased lethality in larval stages suggesting that this two-way compensatory mechanism is essential for growing larvae. Our analyses unravel the importance of Myosin Vb dependent cell size regulation in epidermal homeostasis and demonstrate that the epidermis has the ability to maintain a dynamic balance between cell size and cell number. 相似文献
78.
79.
We report the development of a multiplex, single tube (TaqMan) PCR assay for the identification of three commercially important gadoid species, the cod (Gadus morhua L.), the haddock (Melanogrammus aeglefinus L.) and the whiting (Merlangius merlangus L.). The assay unambiguously identifies known adult tissue samples, and ethanol‐preserved eggs from all three species with greater than 98% accuracy, providing a powerful tool for the development of catch independent stock assessment methods, mapping of spawning sites and the detection of commercial fraud in the fishing and food production industries. 相似文献
80.
Piccoli-Valle Roberta Hilsdorf Brandi Igor Viana Silva Daison Olzany Vieira Passos Frederico José 《World journal of microbiology & biotechnology》2001,17(5):433-437
Penicillium griseoroseum cultured in the presence of sucrose and yeast extract produces pectin lyase (EC 4.2.2.10) (PL) in the absence of its natural inducer pectin. This fungus was cultured in a fermenter at an aeration rate of 0.5 l/min for the first 25 h and 1.0 l/min for the remainder of the culture period, and at a stirring rate of 200 rev/min for the entire culture period. Fungal spores were inoculated directly into the fermenter at a final concentration of 5 × 104 spores/ml. The fungus was cultured in minimal medium supplemented with powdered dehydrated sugar cane juice, producing PL without added yeast extract. Maximum PL activity (0.067 IU/ml) was obtained after 65 h in batch culture. Pellet morphology of the mycelia made it possible to carry out three cycles of repeated batch culture. The same medium was used for renewal as for the single batch culture. The initial cycle was 53 h, after which approximately 0.103 IU/ml of PL was obtained. After this period, the medium was renewed and fermentation continued for two more cycles, which lasted approximately 20 h. Activity of PL obtained in the second cycle was approximately 0.118 IU/ml and in the third, approximately 0.109 IU/ml. 相似文献