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排序方式: 共有377条查询结果,搜索用时 15 毫秒
51.
Beckmann S Leutner S Gouignard N Dissous C Grevelding CG 《Current pharmaceutical design》2012,18(24):3579-3594
Schistosome parasites are the causative pathogens of schistosomiasis (bilharzia), a disease of worldwide significance. In terms of patient numbers, schistosomiasis ranks second to malaria as a parasitosis affecting more than 200 million people of the tropics and subtropics. Since the 1970s Praziquantel (PZQ) is the drug of choice and nearly exclusively used for treatment. However, drug resistance is an increasing threat, particularly with respect to large-scale PZQ administration programs. Last decade's research indicated that resistance against PZQ can be induced under laboratory conditions, and field studies provided first indications for the possibility of reduced PZQ efficacy. Furthermore, clear evidence for the molecular armamentarium of schistosomes with multidrug transporters was found, one of which was responding to PZQ challenge. Also the development of a vaccine still represents an elusive goal, although effort and time have been invested in this subject. In light of these facts it is commonly accepted that new drugs are urgently needed. Research on signal transduction processes in Schistosoma mansoni has provided an unexpected and novel perspective towards this end. Molecular, biochemical, and physiological studies elucidating principles of schistosome development have demonstrated the essential role of protein kinases (PKs). In humans, PKs are known to be involved in cancer development. Since a variety of approved anticancer drugs targeting PKs exist, first studies have been performed to investigate whether these drugs are able to also inhibit schistosome PKs. Indeed, promising results have been obtained indicating the potential of PKs as privileged targets for new concepts in fighting schistosomes. 相似文献
52.
Farouk Belkadi Nadège Troussier Benoit Eynard Eric Bonjour 《International Journal on Interactive Design and Manufacturing》2010,4(3):169-179
The paper proposes a new approach for managing two products lifecycles in the context of collaboration between aircraft OEM
and their equipment suppliers. The concept of entities and specific roles are used to improve the semantic interoperability
between both aircraft and equipment projects’ data. These concepts are also used to formalize the relation between various
processes that guarantee the connection between the aircraft and the assembly equipment lifecycles. The aim of this integration
approach is to enable the information sharing between OEM and suppliers. It intends to enlarge the role of suppliers in the
development process of fixture equipment, which are used in the aircraft assembly process. 相似文献
53.
54.
Limousin N Praline J Motica O Cottier JP Rousselot-Denis C Mokhtari K Gonzalez-Aguilar A De Toffol B 《Journal of neuro-oncology》2012,107(1):223-224
Journal of Neuro-Oncology - 相似文献
55.
Pattern recognition receptors (PRRs) are known for many years for their role in the recognition of microbial products and
the subsequent activation of the immune system. The 2011 Nobel Prize for medicine indeed rewarded J. Hoffmann/B. Beutler and
R. Steinman for their revolutionary findings concerning the activation of the immune system, thus stressing the significance
of understanding the mechanisms of activation of the innate immunity. Such immunostimulatory activities are of major interest
in the context of cancer to induce long-term antitumoral responses. Ligands for the toll-like receptors (TLRs), a well-known
family of PRR, have been shown to have antitumoral activities in several cancers. Those ligands are now undergoing extensive
clinical investigations both as immunostimulant molecules and as adjuvant along with vaccines. However, when considering the
use of these ligands in tumor therapy, one shall consider the potential effect on the tumor cells themselves as well as on
the entire organism. Recent data indeed demonstrate that TLR activation in tumor cells could trigger both pro- or antitumoral
effect depending on the context. This review discusses this balance between the intrinsic activation of PRR in tumor cells
and the extrinsic microenvironment activation in term of overall effect of PRR ligands on tumor development. We review recent
advances in the field and underline appealing prospects for clinical development of PRR agonists in the light of our current
knowledge on their expression and activation. 相似文献
56.
57.
Meiou Dai Amal A Al-Odaini Nadège Fils-Aimé Manuel A Villatoro Jimin Guo Ani Arakelian Shafaat A Rabbani Suhad Ali Jean Jacques Lebrun 《Breast cancer research : BCR》2013,15(3):R49
Introduction
Deregulation of the cell cycle machinery is often found in human cancers. Modulations in the cell cycle regulator function and expression result not only in proliferative advantages, but also lead to tumor progression and invasiveness of the cancer. In particular, cyclin D1 and p21 are often over-expressed in human cancers, correlating with high tumor grade, poor prognosis and increased metastasis. This prompted us to investigate the role of the cyclin D1/p21 signaling axis downstream of transforming growth factor beta (TGFβ) in breast cancer progression.Methods
Cyclins mRNA and protein expressions were assessed by quantitative real-time PCR and Western blot in triple negative breast cancer cell lines. Co-localization and interaction between cyclin D1 and p21 were performed by immunocytochemistry and co-immunoprecipitation, respectively. Cell migration was assessed by wound healing and quantitative time-lapse imaging assays. In addition, the effects of cyclin D1 on cellular structure and actin organization were examined by staining with F-actin marker phalloidin and mesenchymal intermediate filament vimentin. Finally, a mammary fat pad xenograft mouse model was used to assess mammary tumor growth and local invasion.Results
We found TGFβ to specifically up-regulate the expression of cyclin D1 in triple negative breast cancer cells. Induction of cyclin D1 is also required for TGFβ-mediated cell migration. Suppression of cyclin D1 expression not only resulted in a rounded and epithelial-like phenotype, but also prevented TGFβ-induced vimentin and F-actin co-localization at the cell edge as well as invadopodia formation. Furthermore, TGFβ promoted the nuclear co-localization and physical interaction between cyclin D1 and p21. The co-expression of cyclin D1 and p21 proteins are required for the initial steps of tumor development, as double knockdown of these two molecules prevented primary tumor formation in a Xenograft mouse model. Moreover, the in vivo studies indicated that locally advanced features of the invasive tumors, including skeletal muscle, mammary fat pad and lymphovascular invasion, as well as ulcerated skin, were attenuated in the absence of cyclin D1 and p21.Conclusions
Thus, our findings highlight the cyclin D1/p21 signaling axis as a critical regulator of TGFβ-mediated tumor growth initiation and local tumor cell invasion, both in vitro and in vivo. 相似文献58.
Michaud N Al-Akoum M Gagnon G Girard K Blanchet P Rousseau JA Akoum A 《Journal of reproductive immunology》2011,92(1-2):68-73
Interleukin 1 (IL1) may play an important role in endometriosis-associated pelvic inflammation, and natural specific inhibitors, including soluble IL1 receptor accessory protein (sIL1RAcP) and soluble IL1 receptor type 2 (sIL1R2), are critical for counterbalancing the pleiotropic effects of IL1. The objective of this study was to evaluate the levels of sIL1RAcP, together with those of sIL1R2 and IL1β, in the peritoneal fluid of women with and without endometriosis. Peritoneal fluid samples were obtained at laparoscopy and assessed by ELISA. sIL1RAcP concentrations were reduced in endometriosis stages I-II and III-IV. sIL1R2 concentrations were decreased, and those of IL1β were significantly increased in endometriosis stages I-II. sIL1RAcP and sIL1R2 concentrations were significantly decreased in the secretory phase of the menstrual cycle, and IL1β concentrations were elevated in the proliferative and the secretory phases. sIL1RAcP and sIL1R2 concentrations were reduced in women with endometriosis who were infertile, fertile, suffering from pelvic pain or pain-free. However, IL1β concentrations were significantly reduced in women with endometriosis who were infertile or had pelvic pain. These changes may exacerbate the local peritoneal inflammatory reaction observed in women with endometriosis and contribute to endometriosis pathophysiology and the major symptoms of this disease. 相似文献
59.
60.
Nadège Cabrolier Marlène Sauget Xavier Bertrand Didier Hocquet 《Journal of clinical microbiology》2015,53(4):1395-1398
We show here that matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) accurately and quickly identified the five high-risk clones of Pseudomonas aeruginosa sequence type 111 (ST111), ST175, ST235, ST253, and ST395. The use of this screening technique by clinical microbiology laboratories may tackle the spread of high-risk clones by the quick implementation of hygiene control procedures for relevant patients. 相似文献