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排序方式: 共有1429条查询结果,搜索用时 15 毫秒
41.
Lei Yang Jianjun Xu Etsuko Minobe Lifeng Yu Rui Feng Asako Kameyama Kazuto Yazawa Masaki Kameyama 《The journal of physiological sciences : JPS》2013,63(6):419-426
Although Cav1.2 Ca2+ channels are modulated by reactive oxygen species (ROS), the underlying mechanisms are not fully understood. In this study, we investigated effects of hydrogen peroxide (H2O2) on the Ca2+ channel using a patch-clamp technique in guinea pig ventricular myocytes. Externally applied H2O2 (1 mM) increased Ca2+ channel activity in the cell-attached mode. A specific inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII) KN-93 (10 μM) partially attenuated the H2O2-mediated facilitation of the channel, suggesting both CaMKII-dependent and -independent pathways. However, in the inside-out mode, 1 mM H2O2 increased channel activity in a KN-93-resistant manner. Since H2O2-pretreated calmodulin did not reproduce the H2O2 effect, the target of H2O2 was presumably assigned to the Ca2+ channel itself. A thiol-specific oxidizing agent mimicked and occluded the H2O2 effect. These results suggest that H2O2 facilitates the Ca2+ channel through oxidation of cysteine residue(s) in the channel as well as the CaMKII-dependent pathway. 相似文献
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Kondo M Nakata J Arai N Izumo T Tagaya E Takeyama K Tamaoki J Nagai A 《Allergology international》2012,61(1):133-142
Background: Human Ca2 +-activated Cl ion channel 1 (hCLCAl) is expressed in goblet cell hyperplasia in the airway of asthmatics, and murine CLCA3 is associated with antigen-sensitized and IL-13-induced goblet cell metaplasia in mice. However, the role of CLCA in goblet cell degranulation is not fully investigated. Niflumic acid (NFA), a relatively specific CLCA inhibitor, inhibits goblet cell metaplasia, but the effect of NFA on goblet cell degranulation has not been determined in an asthma model.Methods: Guinea pigs were sensitized with ovalbumin (OA) twice and then challenged with saline, OA, histamine, and one of the Ca2 + -dependent secretagogues, UTP. The PAS/AB-stained mucus area in the tracheal epithelium was measured with a computer image analysis system, and the morphology of mucus granules was examined by transmission electron microscopy. In the in vitro experiment, goblet cells cultured with IL-13 at the air-liquid interface were stimulated with UTP in the presence or absence of NFA, and the MUC5AC level in cell lysates was measured by ELISA.Results: The mucus areas were smaller in the OA-, histamine-, and UTP-challenged animals than in the saline-challenged animals. NFA inhibited the decrease in mucus area and morphological changes in mucus granules. UTP caused swelling and exocytosis of mucus granules and MUC5AC secretion by cultured goblet cells, and NFA inhibited these changes.Conclusions: NFA inhibited the secretory response of mucus granules in an asthma model, suggesting that CLCA may be associated with goblet cell degranulation and that CLCA inhibitors may be useful for the treatment of hypersecretion in asthma. 相似文献
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Hirano K Kuratani K Fujiyoshi M Tashiro N Hayashi E Kinoshita M 《Neuroscience letters》2007,412(2):159-162
The taiep rat is a myelin mutant in which immobility episodes (IEs) can be induced in adult males by gripping. EEG recordings during gripping-induced IEs show a rapid eye movement (REM) sleep-like pattern, similar to that reported for narcolepsy-cataplexy suggesting that IEs represent a disorder of REM-sleep. An alpha(2) adrenoceptor agonist increases gripping-induced IEs, whereas alpha(2) antagonists decrease these. We have studied the effect of prazosin on IEs and the levels of alpha(1) adrenoceptors were evaluated in cerebro-cortical homogenates of taiep and control rats. Systemic administration of prazosin results in a significant increase in both the frequency and duration of gripping-induced IEs. Our results show that cerebro-cortical tissue is not an adequate candidate for the expression of cataplexy-like symptoms, but prazosin, an alpha(1) antagonist, is a potent inducer of gripping-induced immobility episodes in taiep rats. 相似文献
47.
Claro S Kanashiro CA Oshiro ME Ferreira AT Khalil RA 《The Journal of pharmacology and experimental therapeutics》2007,322(3):964-972
The use of gamma-radiation in treatment of pelvic cancer is associated with injury of healthy surrounding tissues and disorders of intestinal motility; however, the cellular mechanisms involved are unclear. We tested the hypothesis that exposure of visceral smooth muscle cells (SMCs) to gamma-radiation induces apoptosis via activation of specific protein kinase C (PKC) isoforms. Cultured SMCs and slices from guinea pig ileum smooth muscle longitudinal layer (GPISMLL) were exposed to 10 to 50 Gy. Flow cytometry in gamma-radiated SMCs showed increased percentage of cells in the sub-G(0)/G(1) phase, a hallmark of apoptosis. gamma-Radiation-induced reduction in cell survival was partially but significantly alleviated with the PKC inhibitors. Sections of gamma-irradiated GPISMLL showed DNA fragmentation and apoptotic bodies analyzed by the terminal deoxynucleotidyl transferase dUTP nick-end labeling method, whereas the plasma and nuclear membranes were preserved. Confocal microscopy in gamma-radiated SMCs labeled with annexin V-fluorescein showed an increase in apoptotic cells and phosphatidylserine externalization. Contraction of GPISMLL strips in response to KCl and acetylcholine was reduced in tissues exposed to 30 and 50 Gy. gamma-Radiation of GPISMLL caused an increase in PKC activity in the particulate fraction, a decrease in the cytosolic fraction, and increased particulate/cytosolic PKC activity ratio. Western blot analysis revealed significant amounts of alpha- and epsilon-PKC in the cytosolic fraction of control GPISMLL. gamma-Radiation caused an increase in the amount of alpha- and epsilon-PKC in the particulate fraction and a decrease in the cytosolic fraction. Data suggest that gamma-radiation induces apoptosis, growth arrest, and contractile dysfunction in visceral SMCs of GPISMLL via activation and translocation of alpha- and epsilon-PKC isoforms. 相似文献
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Yoshihiro Dogaki Sang Yang Lee Takahiro Niikura Takashi Iwakura Etsuko Okumachi Takahiro Waki Kenichiro Kakutani Kotaro Nishida Ryosuke Kuroda Masahiro Kurosaka 《International orthopaedics》2014,38(9):1779-1785
Purpose
There has been great interest in the use of induced pluripotent stem cells (iPSCs) in bone regenerative strategies. To generate osteoprogenitor cells from iPSCs, the most widely used protocol relies on an intermediate using embryoid body (EB) formation. We hypothesized that an osteoprogenitor cell population could be efficiently generated from iPSCs by employing a “direct-plating method” without the EB formation step.Methods
Murine iPSC colonies were dissociated with trypsin-EDTA, and obtained single cells were cultured on gelatin-coated plates in MSC medium and FGF-2. Adherent homogeneous fibroblast-like cells obtained by this direct-plating technique were termed as direct-plated cells (DPCs). Expression levels of Oct-3/4 mRNA were analysed by real-time PCR. DPCs were evaluated for cell-surface protein expression using flow cytometry. After osteogenic induction, osteogenic differentiation ability of DPCs was evaluated.Results
The expression level of Oct-3/4 in DPCs was significantly down-regulated compared to that observed in iPSCs, suggesting that the cells lost pluripotency. Flow cytometry analysis revealed that DPCs exhibited cell-surface antigens similar to those of bone marrow stromal cells. Furthermore, the cells proved to have a high osteogenic differentiation capacity, which was confirmed by the significant increase in alkaline phosphatase activity, the expression levels of osteogenic genes, and calcium mineralization after 14-day osteogenic induction.Conclusions
These findings indicate that our novel direct-plating method provides a clinically applicable, simple, and labour-efficient system for generating large numbers of homogeneous iPSC-derived osteoprogenitor cells for bone regeneration. 相似文献50.
Junya Fujita Shuji Takiguchi Kazuhiro Nishikawa Yutaka Kimura Hiroshi Imamura Shigeyuki Tamura Chikara Ebisui Kentaro Kishi Kazumasa Fujitani Yukinori Kurokawa Masaki Mori Yuichiro Doki 《Surgery today》2014,44(9):1723-1729