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排序方式: 共有424条查询结果,搜索用时 31 毫秒
1.
Dongbing Lai Emma C. Johnson Sarah Colbert Gayathri Pandey Grace Chan Lance Bauer Meredith W. Francis Victor Hesselbrock Chella Kamarajan John Kramer Weipeng Kuang Sally Kuo Samuel Kuperman Yunlong Liu Vivia McCutcheon Zhiping Pang Martin H. Plawecki Marc Schuckit Jay Tischfield Leah Wetherill Yong Zang Howard J. Edenberg Bernice Porjesz Arpana Agrawal Tatiana Foroud 《Alcoholism, clinical and experimental research》2022,46(3):374-383
2.
Possible evolution of splice-junction signals in eukaryotic genes from stop codons. 总被引:4,自引:1,他引:3 下载免费PDF全文
P Senapathy 《Proceedings of the National Academy of Sciences of the United States of America》1988,85(4):1129-1133
Splice-junction sequence signals are strongly conserved structural components of eukaryotic genes. These sequences border exon/intron junctions and aid in the process of removing introns by the RNA splicing machinery. Although substantial research has been undertaken to understand the mechanism of splicing, little is known about the origin and evolution of these splice signal sequences. Based on the previously published theory that the primitive genes evolved in pieces from primordial genetic sequences to avoid the interfering stop codons, a "stop-codon walk" mechanism is proposed in this paper to have assisted in the evolution of coding genes. This mechanism predicts the presence of stop codons in splice-junction signals inside the introns. Evidence of the consistent presence of stop codons in the splice-junction signals, in a position where they are expected, is shown by the analysis of codon statistics in these signal sequences in the GenBank databank. The results suggest that the splice-junction signals may have evolved from stop codons as a consequence of a selective pressure to avoid stop codons during the original evolution of coding genes. They also suggest that other splice signals within the introns, such as the branch-point sequence, may have evolved from stop codons for similar reasons. 相似文献
3.
Sanjay Varikuti Chaitenya Verma Gayathri Natarajan Steve Oghumu Abhay R. Satoskar 《The American journal of pathology》2021,191(5):809-816
Interferon (IFN)-γ is indispensable in the resolution of cutaneous leishmaniasis (CL), while the Th2 cytokines IL-4, IL-10, and IL-13 mediate susceptibility. A recent study found that miR155, which promotes CD4+ Th1 response and IFN-γ production, is dispensable in the control of Leishmania donovani infection. Here, the role of miR155 in CL caused by L. major was investigated using miR155-deficient (miR155−/−) mice. Infection was controlled significantly quicker in the miR155−/− mice than in their wild-type (WT) counterparts, indicating that miR155 contributes to the pathogenesis of CL. Faster resolution of infection in miR155−/− mice was associated with increased levels of Th1-associated IL-12 and IFN-γ and reduced production of Th2- associated IL-4, IL-10, and IL-13. Concentrations of IFN-γ+CD8+ T cells and natural killer cells in draining lymph nodes were significantly higher in the L. major−infected miR155−/− mice than in the infected WT mice, as indicated by flow-cytometry. After in vitro IFN-γ stimulation, nitric oxide and IL-12 production were increased, IL-10 production was decreased, and parasite clearance was enhanced in L. major−infected miR155−/− DCs compared to those in WT DCs. Furthermore, IFN-γ production from activated miR155−/− T cells was significantly enhanced in L. major−infected miR155−/− DCs. Together, these findings demonstrate that miR155 promotes susceptibility to CL caused by L. major by promoting Th2 response and inhibiting DC function.Leishmania are obligate intracellular protozoans that infect phagocytes and cause a spectrum of clinical diseases such as cutaneous leishmaniasis (CL) and visceral leishmaniasis. Common in the tropical and subtropical regions, leishmaniasis affects over 1 billion people worldwide, with an incidence of up to 1 million cases per year.1 CL is the most common type of Leishmania infection, manifesting as localized skin lesions that can become chronic, leading to significant tissue destruction and disfigurement.2,3 It is well documented that the induction of a Th1 response and interferon (IFN)-γ are indispensable in the resolution of CL caused by Leishmania major,4 whereas disease progression is associated with the induction of a Th2 response and the production of cytokines such as IL-4 and IL-10.5 Establishing a disease-resolving response in the host is largely dependent on the ability to mount an appropriate Th1 immune response.4 Crucial in this response is the stimulation and activation of DCs that direct T-cell proliferation and differentiation toward IFN-γ–producing Th1 cells.6,7 In addition to activating of phagocytic cells, IFN-γ induces the production of reactive nitrogen species, specifically nitric oxide (NO), leading to enhanced parasite clearance.4miR155 is a recognized regulator of immune cell function and immune response. miR155 enhances macrophage and DC activation and induces inflammatory response,8,9 and up-regulation of miR155 in CD4+ T cells promotes preferential Th1 differentiation and IFN-γ production10 by suppressing the expression of suppressor of cytokine signaling (SOCS)-1.11, 12, 13, 14 Conversely, miR155 gene–deficient mice exhibit diminished levels of Th1/Th17 cells, macrophages, and DCs.15 miR155 has also been shown to play a role in regulating effector Th2 response.16, 17, 18 Collectively, these findings suggest that miR155 regulates both Th1 and Th2 responses, which control the outcome of CL caused by L. major. Therefore, the role of miR155 in immunity to L. major using miR155−/− mice was investigated in the present study. The findings show that miR155 is not required for the induction of a Th1 response and IFN-γ in L. major infection. Rather, miR155 plays a disease-exacerbating role in CL by attenuating DC function and Th1 response and promoting Th2 response. 相似文献
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Gayathri Embuldeniya Jennifer Gutberg Walter P. Wodchis 《Health policy (Amsterdam, Netherlands)》2021,125(1):83-89
Purpose/settingTo encourage clinical and financial efficiency, the Canadian province of Ontario initiated an integrated care program – Integrated Funding Models (IFMs) that required collaboration and coordination across acute and post-acute care sectors. This research shows how program implementers went beyond policy-makers’ original designs, to make integrated care sustainable for chronic diseases.MethodsForty-five interviews were conducted with program participants at three chronic disease programs, as well as with policymakers. Interviews were conducted over two phases; during early implementation in 2016, and as programs matured in 2018. Data were analyzed through a cultural constructivist lens to understand how participants shaped programs.FindingsParticipants desired greater accountability and control. Participants in the first program wanted localized control over decision-making. In the second, participants initiated greater control over financial uncertainty. In the third program, hospital participants sought greater control over community care. Participants across programs simultaneously wanted integrated care to be expanded holistically, spatially, and temporally for patients, extending the length of care, and expanding the spaces in which care was provided. Findings also suggest a gap between program implementers’ and policymakers’ conceptualizations of integrated care.ConclusionThis work shows how IFMs were reimagined in ways that transcended their original conceptualization as spatially and temporally delimited initiatives aimed at improving coordination and efficiency. It has practical implications for those facing sustainability challenges in other contexts. 相似文献
7.
Saravana Kumar Jaganathan Muthu Vignesh Vellayappan Gayathri Narasimhan Eko Supriyanto 《World journal of gastroenterology : WJG》2014,20(16):4618-4625
Colorectal cancer is the second leading cause of cancer-related deaths in the United States.Recent studies prove that though chemotherapeutic agents are being used for the treatment of colon cancer,they become non-effective when the cancer progresses to an invasive stage.Since consumption of certain dietary agents has been linked with various cancers,fruit juices have been investigated for their consistently protective effect against colon cancer.The unique biochemical composition of fruit juices is responsible for their anticancer properties.In this review,the chemo-preventive effect of fruit juices such as pomegranate and citrus juices against colon cancer are discussed.For this purpose,the bioavailability,in vitro and in vivo effects of these fruit juices on colorectal cancer are highlighted.Moreover,there is a scarcity of studies involving human trials to estimate the preventive nature of these juices against colon cancer.This review will support the need for more preclinical tests with these crude juices and their constituents in different colorectal cancer cell lines and also some epidemiological studies in order to have a better understanding and promote pomegranate and citrus juices as crusaders against colon cancer. 相似文献
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Participation of the S4 voltage sensor in the Mg2+-dependent activation of large conductance (BK) K+ channels 下载免费PDF全文
Hu L Shi J Ma Z Krishnamoorthy G Sieling F Zhang G Horrigan FT Cui J 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(18):10488-10493
The S4 transmembrane segment is the primary voltage sensor in voltage-dependent ion channels. Its movement in response to changes in membrane potential leads to the opening of the activation gate, which is formed by a separate structural component, the S6 segment. Here we show in voltage-, Ca2+-, and Mg2+-dependent, large conductance K+ channels that the S4 segment participates not only in voltage- but also Mg2+-dependent activation. Mutations in S4 and the S4-S5 linker alter voltage-dependent activation and have little or no effect on activation by micromolar Ca2+. However, a subset of these mutations in the C-terminal half of S4 and in the S4-S5 linker either reduce or abolish the Mg2+ sensitivity of channel gating. Cysteine residues substituted into positions R210 and R213, marking the boundary between S4 mutations that alter Mg2+ sensitivity and those that do not, are accessible to a modifying reagent [sodium (2-sulfonatoethyl)methane-thiosulfonate] (MTSES) from the extracellular and intracellular side of the membrane, respectively, at -80 mV. This implies that interactions between S4 and a cytoplasmic domain may be involved in Mg2+-dependent activation. These results indicate that the voltage sensor is critical for Mg2+-dependent activation and the coupling between the voltage sensor and channel gate is a converging point for voltage- and Mg2+-dependent activation pathways. 相似文献