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OBJECTIVES: To determine whether weather conditions explain the North-South gradient in multiple sclerosis (MS) mortality described in Spain. METHODS: The age-adjusted MS mortality rate by Spanish provinces from 1975 to 1998 was correlated with several climatic variables. RESULTS: MS mortality was negatively correlated with minimum, average and maximum temperatures, the mean number of hours of sunshine, and the mean number of sunny days. A positive correlation was found with the average amount of rain. Most correlations disappeared after adjusting by latitude. However, MS mortality was associated with latitude after adjusting by climatic factors. CONCLUSIONS: The North-South gradient in MS mortality in Spain cannot be fully explained by weather differences. Therefore, other hypotheses are required to explain this association. 相似文献
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Functional and structural characterization of four mouse monoclonal antibodies to complement C3 with potential therapeutic and diagnostic applications
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Adrián Martín‐Ambrosio Mercedes Domínguez Agustin Tortajada Santiago Rodríguez de Córdoba Oscar Llorca 《European journal of immunology》2017,47(3):504-515
C3 is the central component of the complement system. Upon activation, C3 sequentially generates various proteolytic fragments, C3a, C3b, iC3b, C3dg, each of them exposing novel surfaces, which are sites of interaction with other proteins. C3 and its fragments are therapeutic targets and markers of complement activation. We report the structural and functional characterization of four monoclonal antibodies (mAbs) generated by immunizing C3‐deficient mice with a mixture of human C3b, iC3b and C3dg fragments, and discuss their potential applications. This collection includes three mAbs interacting with native C3 and inhibiting AP complement activation; two of them by blocking the cleavage of C3 by the AP C3‐converase and one by impeding formation of the AP C3‐convertase. The interaction sites of these mAbs in the target molecules were determined by resolving the structures of Fab fragments bound to C3b and/or iC3b using electron microscopy. A fourth mAb specifically recognizes the iC3b, C3dg, and C3d fragments. It binds to an evolutionary‐conserved neoepitope generated after C3b cleavage by FI, detecting iC3b/C3dg deposition over opsonized surfaces by flow cytometry and immunohistochemistry in human and other species. Because well‐characterized anti‐complement mAbs are uncommon, the mAbs reported here may offer interesting therapeutic and diagnostic opportunities. 相似文献
157.
Type 2A von Willebrand disease (vWD), the most common qualitative form of vWD, is characterized by a relative decrease in circulating intermediate and high molecular weight (HMW) multimers. We studied the biosynthesis of recombinant von Willebrand factor (vWF) containing each of two type 2A vWD mutations previously reported by us, Arg834Gln and Val902Glu. The structure of recombinant Arg834Gln vWF within transfected COS-7 cells and the secretion of HMW multimers were similar to wild type vWF. The normal transport and secretion of Arg834Gln vWF, categorizes it as a group II type 2A mutation. In contrast, the Val90- 2Glu mutation resulted in intracellular proteolysis of vWF with the generation of a 176-kD fragment and retention of vWF between the endoplasmic reticulum and the Golgi complex. Moreover, the 176-kD fragment was also increased in plasma from patients with the Val902Glu mutation. Significantly impaired secretion and intracellular proteolysis of Val902Glu vWF categorizes a new sub-group of type 2A mutations. The intracellular proteolysis of vWF Val902Glu explains the lack of response to 1-deamino 8-D-arginine vasopressin (DDAVP) in patients who carry the mutation. 相似文献
158.
Role of Toll‐like receptor 9 signaling on activation of nasal polyp–derived fibroblasts and its association with nasal polypogenesis
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Soo Kyoung Park MD Soung Yong Jin MD PhD Sun Hee Yeon PM Sung Bok Lee MD PhD Jun Xu MD PhD Young Hoon Yoon MD Ki Sang Rha MD PhD Yong Min Kim MD PhD 《International forum of allergy & rhinology》2018,8(9):1001-1012
Background
Nasal polyposis is characterized by persistent inflammation and remodeling in sinonasal mucosa. Toll‐like receptor 9 (TLR9) is a DNA receptor of the innate immune system that plays a pivotal role in fibrosis and inflammatory responses. The aim of this study is to explore the expression, activity, and potential pathogenic role of TLR9 signaling in tissue remodeling in nasal polyp–derived fibroblasts (NPDFs).Methods
Fibrotic and inflammatory responses elicited by type A CpG oligonucleotides were examined in the NPDFs by a combination of real‐time quantitative polymerase chain reaction, Western blot analysis, enzyme‐linked immunosorbent assay, and immunofluorescence staining. For these experiments, the NPDFs were stimulated with different TLR9 agonists (CpG A and B) and blocked with inhibitors (MyD88 inhibitor and chloroquine).Results
TLR9 expression was significantly higher in nasal polyposis (NP) tissues compared to control or chronic rhinosinusitis (CRS) mucosa. In the NPDFs, TLR9 showed intracellular localization and expression of TLR9 was increased after treatment with CpG A. CpG A increased production of α‐smooth muscle actin (α‐SMA), fibronectin, and matrix metalloproteinases (MMPs) (MMP1, MMP2, and MMP9) in the NPDFs, while MyD88 inhibitor and chloroquine, which are known to block the TLR9 signaling pathway, inhibited their production. CpG A also produced type I interferons (IFN‐α and IFN‐β), which were inhibited by MyD88 inhibitor.Conclusion
Our data indicates that CpG A–induced fibroblast activation and cytokine production were mediated via TLR9 stimulation in NPDFs. Disrupting this process with an inhibitor targeting TLR9 or its downstream signaling pathways could represent a novel approach to CRS with NP (CRSwNP) therapy.159.
Kyriaki Papantoniou Gemma Castaño‐Vinyals Ana Espinosa Nuria Aragonés Beatriz Pérez‐Gómez Javier Burgos Inés Gómez‐Acebo Javier Llorca Rosana Peiró Jose Juan Jimenez‐Moleón Francisco Arredondo Adonina Tardón Marina Pollan Manolis Kogevinas 《International journal of cancer. Journal international du cancer》2015,137(5):1147-1157
Night shift work has been classified as a probable human carcinogen based on experimental studies and limited human evidence on breast cancer. Evidence on other common cancers, such as prostate cancer, is scarce. Chronotype is an individual characteristic that may relate to night work adaptation. We evaluated night shift work with relation to prostate cancer, taking into account chronotype and disease severity in a population based case‐control study in Spain. We included 1,095 prostate cancer cases and 1,388 randomly selected population controls. We collected detailed information on shift schedules (permanent vs. rotating, time schedules, duration, frequency), using lifetime occupational history. Sociodemographic and lifestyle factors were assessed by face‐to‐face interviews and chronotype through a validated questionnaire. We used unconditional logistic regression analysis adjusting for potential confounders. Subjects who had worked at least for one year in night shift work had a slightly higher prostate cancer risk [Odds Ratio (OR) 1.14; 95%CI 0.94, 1.37] compared with never night workers; this risk increased with longer duration of exposure (≥28 years: OR 1.37; 95%CI 1.05, 1.81; p‐trend = 0.047). Risks were more pronounced for high risk tumors [D'Amico classification, Relative Risk Ratio (RRR) 1.40; 95%CI 1.05, 1.86], particularly among subjects with longer duration of exposure (≥28 years: RRR 1.63; 95%CI 1.08, 2.45; p‐trend = 0.027). Overall risk was higher among subjects with an evening chronotype, but also increased in morning chronotypes after long‐term night work. In this large population based study, we found an association between night shift work and prostate cancer particularly for tumors with worse prognosis. 相似文献
160.
de Pedro María Baeza Sara Escudero María-Teresa Dierssen-Sotos Trinidad Gómez-Acebo Inés Pollán Marina Llorca Javier 《Breast cancer research and treatment》2015,149(2):525-536
Breast Cancer Research and Treatment - Evidence on non-steroidal anti-inflammatory drugs (NSAID) use and breast cancer risk shows a slightly protective effect of these drugs, but previous studies... 相似文献