全文获取类型
收费全文 | 11490篇 |
免费 | 749篇 |
国内免费 | 62篇 |
专业分类
耳鼻咽喉 | 106篇 |
儿科学 | 331篇 |
妇产科学 | 237篇 |
基础医学 | 1664篇 |
口腔科学 | 255篇 |
临床医学 | 1015篇 |
内科学 | 2648篇 |
皮肤病学 | 425篇 |
神经病学 | 1160篇 |
特种医学 | 263篇 |
外科学 | 942篇 |
综合类 | 57篇 |
现状与发展 | 1篇 |
一般理论 | 3篇 |
预防医学 | 1365篇 |
眼科学 | 226篇 |
药学 | 783篇 |
中国医学 | 52篇 |
肿瘤学 | 768篇 |
出版年
2024年 | 6篇 |
2023年 | 133篇 |
2022年 | 263篇 |
2021年 | 507篇 |
2020年 | 261篇 |
2019年 | 431篇 |
2018年 | 524篇 |
2017年 | 318篇 |
2016年 | 306篇 |
2015年 | 376篇 |
2014年 | 529篇 |
2013年 | 645篇 |
2012年 | 986篇 |
2011年 | 957篇 |
2010年 | 562篇 |
2009年 | 457篇 |
2008年 | 724篇 |
2007年 | 717篇 |
2006年 | 613篇 |
2005年 | 660篇 |
2004年 | 560篇 |
2003年 | 523篇 |
2002年 | 464篇 |
2001年 | 83篇 |
2000年 | 41篇 |
1999年 | 83篇 |
1998年 | 80篇 |
1997年 | 64篇 |
1996年 | 60篇 |
1995年 | 50篇 |
1994年 | 29篇 |
1993年 | 40篇 |
1992年 | 29篇 |
1991年 | 24篇 |
1990年 | 18篇 |
1989年 | 10篇 |
1988年 | 16篇 |
1987年 | 10篇 |
1986年 | 7篇 |
1985年 | 8篇 |
1984年 | 15篇 |
1983年 | 14篇 |
1982年 | 7篇 |
1981年 | 10篇 |
1980年 | 7篇 |
1979年 | 6篇 |
1978年 | 7篇 |
1977年 | 6篇 |
1974年 | 6篇 |
1968年 | 4篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
81.
Major histocompatibility complex status in breast carcinogenesis and relationship to apoptosis 总被引:2,自引:0,他引:2
Redondo M García J Villar E Rodrigo I Perea-Milla E Serrano A Morell M 《Human pathology》2003,34(12):1283-1289
Major histocompatibility complex (MHC) molecules are of central importance in regulating the immune response against tumors. In this study we used immunohistochemistry to study human leukocyte antigen (HLA) class I and II antigen expression in normal breast tissues and benign, preneoplastic, primary, and metastatic breast lesions using antibodies against beta-2-microglobulin (beta2-m), heavy-chain, and HLA-DR antigens. Whereas all normal tissues and benign lesions were positive for beta2-m and HLA-A, -B, and -C antigens, total loss of HLA class I antigens was found in 37% (11 of 30) of in situ carcinomas, in 43% (56 of 131) of the primary tumors, and in 70% (31 of 45) of the lymph node metastases. HLA-DR was also underexpressed in breast cancer cells; thus 20% (6 of 30) of in situ carcinomas, 15% of invasive carcinomas (20 of 131), and only 1 metastatic case were positive for this antigen. Both HLA class I and II antigen expression were more frequently down-regulated in metastatic lesions than in primary breast lesions (P <0.05), and a tendency toward a simultaneous defective expression of HLA class I and II antigens was observed in primary carcinomas (P = 0.07). However, no correlation was found between the expression of any of the aforementioned molecules and pathological parameters or survival. Interestingly, HLA class I expression was expressed more frequently in tissues with high apoptotic activity and was significantly associated with the expression of the proapoptotic bax gene (P = 0.02), and was inversely associated with expression of the antiapoptotic bcl-2 gene (P = 0.03). We conclude that alterations in HLA class I and II antigen expression are early events in breast carcinogenesis and play significant roles in metastatic progression. In addition, their expression is correlated with apoptosis-regulating proteins, which may influence the cytotoxicity of T cells against HLA class I-specific tumor antigens. 相似文献
82.
The three types (groups I, II and III) of stable extracellular 14 kDa phospholipase A2 enzymes differ in their primary amino acid sequences and their properties. It may thus be possible to design low-molecular weight inhibitors targeted to the secretory form of mammalian PLA2. this enzyme has been implicated in inflammatory disorders. We have studied the inhibition of four distinct PLA2 enzymes by a range of NSAIDs, using3H-oleate release from prelabelled membranes ofE. coli for assay. The enzymes used were cobra venom PLA2 (Naja naja, a group I enzyme), bee venom PLA2 (Apis mellifera, group III), recombinant human synovial PLA2 (group II) and rat peritoneal PLA2 (group II). Under the conditions of the3H-oleateE. coli assay, 1 mM concentrations of aspirin, sodium salicylate, paracetamol (acetaminophen), oxphenbutazone, ibuprofen, flurbiprofen and nabumetone failed to inhibit significantly any of the four enzymes. However, indomethacin inhibited all four enzymes, although effects were greatest on the two group II enzymes (rat peritoneal and human synovial PLA2). Approximate IC50 values were 28 and 35 M, respectively. Inhibition by indomethacin was not time dependent and was greater at micromolar rather than millimolar levels of calcium. We conclude that indomethacin but not the other tested classes of NSAID inhibits the group II PLA2 enzyme in a selective manner and suggest that this may be relevant both to its clinical spectrum and to the design of novel pharmaceutical leads. 相似文献
83.
J. R. S. Hoult Robert A. Forder Beatriz de las Heras Isabel B. Lobo Miguel Payá 《Inflammation research》1994,42(1-2):44-49
Sixteen plant-derived or synthetic coumarins with different patterns of substitution were tested for their capacity to modify A23187-induced synthesis of leukotriene B4 and thromboxane B2 via the 5-lipoxygenase and cyclooxygenase pathways of arachidonate metabolism in rat peritoneal exudate leukocytes. Five of the 16 coumarins inhibited LTB4 production: all containortho-dihydroxy substitutions (approximate IC50 values 8–100 M). The mechanism is likely to depend upon a combination of the coumarins' iron-chelating and iron ion-reducing abilities, properties which also confer beneficial activities of these compounds as scavengers of reactive oxygen species (Payá et al., Biochem. Pharmacol.44, 205–214 (1992)). Inhibition of the cyclooxygenase pathway was only demonstrated by one compound, 5,7-dihydroxy-4-methylcoumarin, which did not inhibit 5-lipoxygenase, indicating that the cyclooxygenase inhibitory mechanism is different. Similar effects of the active coumarins were obtained using arachidonic acid as substrate for rat leukocyte eicosanoid generation, confirming that they act at the 5-lipoxygenase/cyclooxygenase level. The same profile of activity was also shown when the coumarins were tested against 5-lipoxygenase in human polymorphonuclear neutrophils. Taken together, these antioxidant and anti-eicosanoid properties of coumarins could be exploited for the design of potentially valuable non-toxic anti-inflammatory agents for treating diseases in which eicosanoid generation and the production of reactive oxygen species are involved. 相似文献
84.
Amene Tesfaye Alba Rodríguez-Nogales Sara Benedé Tahía D. Fernández Juan L. Paris Maria J. Rodriguez Isabel M. Jiménez-Sánchez Gador Bogas Cristobalina Mayorga María J. Torres María I. Montañez 《Allergy》2021,76(10):3183-3193
Background
Amoxicillin (AX) is nowadays the β-lactam that more frequently induces immediate allergic reactions. Nevertheless, diagnosis of AX allergy is occasionally challenging due to risky in vivo tests and non-optimal sensitivity of in vitro tests. AX requires protein haptenation to form multivalent conjugates with increased size to be immunogenic. Knowing adduct structural features for promoting effector cell activation would help to improve in vitro tests. We aimed to identify the optimal structural requirement in specific cellular degranulation to AX using well-precised nanoarchitectures of different lengths.Method
We constructed eight Bidendron Antigens (BiAns) based on polyethylene glycol (PEG) linkers of different lengths (600–12,000 Da), end-coupled with polyamidoamine dendrons that were terminally multi-functionalized with amoxicilloyl (AXO). In vitro IgE recognition was studied by competitive radioallergosorbent test (RAST) and antibody–nanoarchitecture complexes by transmission electron microscopy (TEM). Their allergenic activity was evaluated using bone marrow-derived mast cells (MCs) passively sensitized with mouse monoclonal IgE against AX and humanized RBL-2H3 cells sensitized with polyclonal antibodies from sera of AX-allergic patients.Results
All BiAns were recognized by AX-sIgE. Dose-dependent activation responses were observed in both cellular assays, only with longer structures, containing spacers in the range of PEG 6000–12,000 Da. Consistently, greater proportion of immunocomplexes and number of antibodies per complex for longer BiAns were visualized by TEM.Conclusions
BiAns are valuable platforms to study the mechanism of effector cell activation. These nanomolecular tools have demonstrated the importance of the adduct size to promote effector cell activation in AX allergy, which will impact for improving in vitro diagnostics.85.
Teruya Cheryl Joshi Vandana Urada Darren Trabin Tom Iturrios-Fourzan Isabel Huang Yu-Chuang 《The journal of behavioral health services & research》2022,49(2):190-203
The Journal of Behavioral Health Services & Research - Statistical reliability of the Treatment Perceptions Survey (TPS) questionnaire was examined using data from 19 California counties. The... 相似文献
86.
Daniel Gonzlez-Hedstrm Teresa Priego Asuncin Lpez-Caldern Sara Amor María de la Fuente-Fernndez Antonio Manuel Inarejos-García ngel Luis García-Villaln Ana Isabel Martín Miriam Granado 《Nutrients》2021,13(1)
Aging is associated with a progressive decline in skeletal muscle mass, strength and function (sarcopenia). We have investigated whether a mixture of algae oil (25%) and extra virgin olive oil (75%) could exert beneficial effects on sarcopenia. Young (3 months) and old (24 months) male Wistar rats were treated with vehicle or with the oil mixture (OM) (2.5 mL/kg) for 21 days. Aging decreased gastrocnemius weight, total protein, and myosin heavy chain mRNA. Treatment with the OM prevented these effects. Concomitantly, OM administration decreased the inflammatory state in muscle; it prevented the increase of pro-inflammatory interleukin-6 (IL-6) and the decrease in anti-inflammatory interleukin-10 (IL-10) in aged rats. The OM was not able to prevent aging-induced alterations in either the insulin-like growth factor I/protein kinase B (IGF-I/Akt) pathway or in the increased expression of atrogenes in the gastrocnemius. However, the OM prevented decreased autophagy activity (ratio protein 1A/1B-light chain 3 (LC3b) II/I) induced by aging and increased expression of factors related with muscle senescence such as histone deacetylase 4 (HDAC-4), myogenin, and IGF-I binding protein 5 (IGFBP-5). These data suggest that the beneficial effects of the OM on muscle can be secondary to its anti-inflammatory effect and to the normalization of HDAC-4 and myogenin levels, making this treatment an alternative therapeutic tool for sarcopenia. 相似文献
87.
Isabel Campos-Varela Oscar Len Ares Villagrasa Ester Márquez-Algaba Juliana Esperalba Cristina Dopazo Ibai Los-Arcos Andrés Antón Lluís Castells 《Transplant international》2021,34(10):1908-1913
Solid organ transplant recipients might be at greater risk for acquisition and mortality because of SARS-CoV-2. There are no data regarding SARS-CoV-2 seroprevalence among liver transplant (LT) recipients, and whether it is different from that of the general population or other immunosuppressed groups. We evaluated the prevalence of IgG SARS-CoV-2 antibodies among LT recipients to estimate the frequency of asymptomatic SARS-CoV-2 infection using serological assays in our outpatient clinic. We conducted a cross-sectional analysis from 10 May to 26 October 2020 of all adult (>18 years) LT recipients that underwent a routine laboratory test for the outpatient clinic follow-up at the Hospital Universitari Vall d’Hebron (Barcelona) in which we included serological testing for SARS-CoV-2. Nine out of 294 LT recipients (3.1%) tested positive for anti-SARS-CoV-2 IgG antibodies. Five of them (55.5%) had suffered clinically symptomatic SARS-CoV-2 infection confirmed by RT-PCR, four (44.4%) had presented compatible symptoms but without microbiological confirmation and only one patient (1/9, 11.1%) tested positive without any previous symptom. SARS-CoV-2 seroprevalence among LT recipients in an area highly affected by the pandemic is lower than in the general population in the same area. These results render the possibility of asymptomatic infection in LT recipients very unlikely. 相似文献
88.
Isabel M. A. Brüggenwirth Maureen J. M. Werner René Adam Wojciech G. Polak Vincent Karam Michael A. Heneghan Arianeb Mehrabi Jürgen L. Klempnauer Andreas Paul Darius F. Mirza Johann Pratschke Mauro Salizzoni Daniel Cherqui Michael Allison Olivier Soubrane Steven J. Staffa David Zurakowski Robert J. Porte Vincent E. de Meijer all the other contributing centers the European Liver Intestine Transplant Association 《Transplant international》2021,34(10):1928-1937
High-risk combinations of recipient and graft characteristics are poorly defined for liver retransplantation (reLT) in the current era. We aimed to develop a risk model for survival after reLT using data from the European Liver Transplantation Registry, followed by internal and external validation. From 2006 to 2016, 85 067 liver transplants were recorded, including 5581 reLTs (6.6%). The final model included seven predictors of graft survival: recipient age, model for end-stage liver disease score, indication for reLT, recipient hospitalization, time between primary liver transplantation and reLT, donor age, and cold ischemia time. By assigning points to each variable in proportion to their hazard ratio, a simplified risk score was created ranging 0–10. Low-risk (0–3), medium-risk (4–5), and high-risk (6–10) groups were identified with significantly different 5-year survival rates ranging 56.9% (95% CI 52.8–60.7%), 46.3% (95% CI 41.1–51.4%), and 32.1% (95% CI 23.5–41.0%), respectively (P < 0.001). External validation showed that the expected survival rates were closely aligned with the observed mortality probabilities. The Retransplantation Risk Score identifies high-risk combinations of recipient- and graft-related factors prognostic for long-term graft survival after reLT. This tool may serve as a guidance for clinical decision-making on liver acceptance for reLT. 相似文献
89.
Molecular and Cellular Mechanisms of Delayed Fracture Healing in Mmp10 (Stromelysin 2) Knockout Mice
José Valdés-Fernández Tania López-Martínez Purificación Ripalda-Cemboráin Isabel A Calvo Borja Sáez Juan Antonio Romero-Torrecilla Javier Aldazabal Emma Muiños-López Verónica Montiel Josune Orbe José Antonio Rodríguez José Antonio Páramo Felipe Prósper Froilán Granero-Moltó 《Journal of bone and mineral research》2021,36(11):2203-2213
The remodeling of the extracellular matrix is a central function in endochondral ossification and bone homeostasis. During secondary fracture healing, vascular invasion and bone growth requires the removal of the cartilage intermediate and the coordinate action of the collagenase matrix metalloproteinase (MMP)-13, produced by hypertrophic chondrocytes, and the gelatinase MMP-9, produced by cells of hematopoietic lineage. Interfering with these MMP activities results in impaired fracture healing characterized by cartilage accumulation and delayed vascularization. MMP-10, Stromelysin 2, a matrix metalloproteinase with high homology to MMP-3 (Stromelysin 1), presents a wide range of putative substrates identified in vitro, but its targets and functions in vivo and especially during fracture healing and bone homeostasis are not well defined. Here, we investigated the role of MMP-10 through bone regeneration in C57BL/6 mice. During secondary fracture healing, MMP-10 is expressed by hematopoietic cells and its maximum expression peak is associated with cartilage resorption at 14 days post fracture (dpf). In accordance with this expression pattern, when Mmp10 is globally silenced, we observed an impaired fracture-healing phenotype at 14 dpf, characterized by delayed cartilage resorption and TRAP-positive cell accumulation. This phenotype can be rescued by a non-competitive transplant of wild-type bone marrow, indicating that MMP-10 functions are required only in cells of hematopoietic linage. In addition, we found that this phenotype is a consequence of reduced gelatinase activity and the lack of proMMP-9 processing in macrophages. Our data provide evidence of the in vivo function of MMP-10 during endochondral ossification and defines the macrophages as the lead cell population in cartilage removal and vascular invasion. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). 相似文献
90.