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11.
Regeneration of defects in articular cartilage in rat knee joints by CCN2 (connective tissue growth factor). 总被引:7,自引:0,他引:7
Takashi Nishida Satoshi Kubota Shunji Kojima Takuo Kuboki Kyouji Nakao Toshihiro Kushibiki Yasuhiko Tabata Masaharu Takigawa 《Journal of bone and mineral research》2004,19(8):1308-1319
CTGF/CCN2, a hypertrophic chondrocyte-specific gene product, possessed the ability to repair damaged articular cartilage in two animal models, which were experimental osteoarthritis and full-thickness defects of articular cartilage. These findings suggest that CTGF/CCN2 may be useful in regeneration of articular cartilage. INTRODUCTION: Connective tissue growth factor (CTGF)/CCN2 is a unique growth factor that stimulates the proliferation and differentiation, but not hypertrophy, of articular chondrocytes in vitro. The objective of this study was to investigate the therapeutic use of CTGF/CCN2. MATERIALS AND METHODS: The effects of recombinant CTGF/CCN2 (rCTGF/CCN2) on repair of damaged cartilage were evaluated by using both the monoiodoacetic acid (MIA)-induced experimental rat osteoarthritis (OA) model and full-thickness defects of rat articular cartilage in vivo. RESULTS: In the MIA-induced OA model, quantitative real-time RT-PCR assays showed a significant increase in the level of CTGF/CCN2 mRNA, and immunohistochemical analysis and in situ hybridization revealed that the clustered chondrocytes, in which clustering indicates an attempt to repair the damaged cartilage, produced CTGF/CCN2. Therefore, CTGF/CCN2 was suspected to play critical roles in cartilage repair. In fact, a single injection of rCTGF/CCN2 incorporated in gelatin hydrogel (rCTGF/CCN2-hydrogel) into the joint cavity of MIA-induced OA model rats repaired their articular cartilage to the extent that it became histologically similar to normal articular cartilage. Next, to examine the effect of rCTGF/CCN2 on the repair of articular cartilage, we created defects (2 mm in diameter) on the surface of articular cartilage in situ and implanted rCTGF/CCN2-hydrogel or PBS-hydrogel therein with collagen sponge. In the group implanted with rCTGF/CCN2-hydrogel collagen, new cartilage filled the defect 4 weeks postoperatively. In contrast, only soft tissue repair occurred when the PBS-hydrogel collagen was implanted. Consistent with these in vivo effects, rCTGF/CCN2 enhanced type II collagen and aggrecan mRNA expression in mouse bone marrow-derived stromal cells and induced chondrogenesis in vitro. CONCLUSION: These findings suggest the utility of CTGF/CCN2 in the regeneration of articular cartilage. 相似文献
12.
E Ohshima H Takami H Sato S Mohri H Obase I Miki A Ishii S Shirakura A Karasawa K Kubo 《Journal of medicinal chemistry》1992,35(18):3402-3413
A series of 11-[2-(1-benzimidazolyl)ethylidene]-6,11-dihydrodibenz[b,e]oxep in-2- carboxylic acid derivatives and related compounds were synthesized and found to be potent TXA2/PGH2 receptor antagonists. Each compound synthesized was tested for its ability to displace [3H]U-46619 binding from guinea pig platelet TXA2/PGH2 receptors. Structure-activity relationship studies revealed that the following key elements were required for enhanced activities: (1) an (E)-2-(1-benzimidazolyl)ethylidene side chain in the 11-position of the dibenzoxepin ring system and (2) a carboxyl group in the 2-position of the dibenzoxepin ring system. The studies also indicated that the TXA2/PGH2 receptor binding affinities of this series of compounds in guinea pig platelet were poorly correlated with those in human platelet. Introduction of substituent(s) to the benzimidazole moiety was effective and sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl)ethylidene]- 6,11-dihydrodibenz[b,e]oxepin-2-carboxylate monohydrate (57) recorded the highest affinity for human platelet TXA2/PGH2 receptor with a K(i) value of 1.2 +/- 0.14 nM. It demonstrated potent inhibitory effects on U-46619-induced guinea pig platelet aggregation (in vitro and ex vivo) and human platelet aggregation (in vitro). Compound 57, now designated as KW-3635, is a novel, orally active, and specific TXA2/PGH2 receptor antagonist with neither TXA2/PGH2 receptor agonistic nor TXA2 synthase inhibitory effects. It is now under clinical evaluation. 相似文献
13.
Tatsuya Okimoto Hiroshi Yahata Yasuhiko Fukuda Keisuke Hayamizu Kiyohiko Dohi 《Transplant international》1994,7(S1):629-633
Abstract A study was conducted to elucidate the mechanism of donor-pecific Mixed Lymphocyte Reaction (MLR and Cell Mediated Lymphotoxicity (CML) unresponsiveness in a renal transplant recipient with a long-term well-functioning kidney. The peripheral blood lymphocytes (PBL) of the recipient, who had not shown rejection since his transplantation 5 years previously, and those of his mother (donor), his father and two healthy third parties were examined. MLR, CML, semimicro MLR in a double chamber, interleukin-2 (IL-2) synthesis assay and limiting dilution assay were performed. This recipient showed donor-pecific MLR and CML unresponsiveness. IL-2 assay showed that the PBL of the recipient produced less IL-2 against the donor than against the father and the third parties. The addition of exogenous recombinant IL-2 (rIL-2; Takeda Co.) to the priming MLR caused a recovery of CML against the donor. A limiting dilution assay indicated that cytotoxic T cell precursor (CTLp) frequencies against the donor and father did not differ. The suppressor assay in a double chamber indicated that the PBL of the recipient stimulated by the donor PBL had a non-pecific suppressive effect on MLR, CML and IL-2 synthesis of the PBL across the Major Histocompatibility Complex (MHC) barrier. This suppressive effect was abolished by OKT3 or OKT8 monoclonal antibody and complement. Thus, the recipient had donor-pecific suppressor T cells that produced a humoral non-pecific suppressive factor only when stimulated by the donor PBL, and this factor suppressed PLR and CML by inhibiting IL-2 synthesis of the PBL. 相似文献
14.
Takuya Onizuka M.D. Noriyoshi Sumiya M.D. Ryosuke Aoyama M.D. Yasuhiko Fukuya M.D. Takao Jinnai M.D. 《Aesthetic plastic surgery》1990,14(1):207-213
The results of repairing cleft lip by aesthetic plastic surgery are now excellent. However, the cleft lipnose deformity is still very difficult to repair with the present techniques. A technique that can repair the cleft lip-nose deformity with good results is presented. The technique is divided into three parts: Part I consists of nasal repair of the primary cleft lip. Part II is nasal reconstruction as a secondary operation with or without lip repair. For example, nasal reconstruction may be secondary to repair of deformities of the sill, rim, limen nasi, septum, or nasal bones. Part III is an aesthetic nasal operation such as rhinoplasty, mentoplasty, or zygomaplasty. 相似文献
15.
Mitsuru Masaki Tadashi Kuroda Naoki Hosen Hisao Hirota Kazuo Terai Yuichi Oshima Yoshikazu Nakaoka Shoko Sugiyama Ryusuke Kimura Satoshi Yoshihara Manabu Kawakami Norishige Iizuka Yasuhiko Tomita Hiroyasu Ogawa Ichiro Kawase Keiko Yamauchi-Takihara 《Journal of the American Society of Echocardiography》2004,17(4):397-398
A 57-year-old man with a history of renal cell carcinoma presented with presyncope. He underwent nephrectomy years earlier followed by HLA-matched allogeneic peripheral-blood stem-cell transplantation. Echocardiographic investigation revealed a solitary right ventricle mass without contiguous vena caval or right atrial involvement. The mass was pathologically confirmed to be metastatic carcinoma in the right ventricular cavity. This case highlights the need to consider an underlying neoplastic syndrome in patients presenting isolated right ventricle mass by echocardiography. 相似文献
16.
Pharmacologic preconditioning effects: Prostaglandin E1 induces heat-shock proteins immediately after ischemia/reperfusion of the mouse liver 总被引:1,自引:0,他引:1
Ken-ichi Matsuo M.D. Shinji Togo M.D. Ph.D. Hitoshi Sekido M.D. Ph.D. Tomoyuki Morita M.D. Ph.D. Masako Kamiyama Ph.D. Daisuke Morioka M.D. Ph.D. Toru Kubota M.D. Ph.D. Yasuhiko Miura M.D. Ph.D. Kuniya Tanaka M.D. Ph.D. Takashi Ishikawa M.D. Ph.D. Yasushi Ichikawa M.D. Ph.D. Itaru Endo M.D. Ph.D. Hitoshi Goto M.D. Ph.D. Hiroyuki Nitanda M.D. Ph.D. Yasushi Okazaki M.D. Ph.D. Yoshihide Hayashizaki M.D. Ph.D. Hiroshi Shimada M.D. Ph.D. 《Journal of gastrointestinal surgery》2005,9(6):758-768
Prostaglandin E1 (PGE1) has several potential therapeutic effects, including cytoprotection, vasodilation, and inhibition of platelet aggregation. This study investigates the protective action of PGE1 against hepatic ischemia/reperfusion injury in vivo using a complementary DNA microarray. PGE1 or saline was continuously administered intravenously to mice in which the left lobe of the liver was made ischemic for 30 minutes and then reperfused. Livers were harvested 0, 10, and 30 minutes postreperfusion. Messenger RNA was extracted, and the samples were labeled with two different fluorescent dyes and hybridized to the RIKEN set of 18,816 full-length enriched mouse complementary DNA microarrays. Serum alanine aminotransferase and aspartate aminotransferase levels at 180 minutes postreperfusion were significantly lower in the PGE1-treated group than in the saline-treated group. The cDNA microarray analysis revealed that the genes encoding heat-shock protein (HSP) 70, glucose-regulated protein 78, HSP86, and glutathione S-transferase were upregulated at the end of the ischemic period (0 minutes postreperfusion) in the PGE1 group. Our results suggested that PGE1 induces HSPs immediately after ischemia reperfusion. HSPs might therefore play an important role in the protective effects of PGE1 against ischemia/reperfusion injury of the liver. 相似文献
17.
Tsuneo Namba Hongxi Xu Shigetoshi Kadota Masao Hattori Tooru Takahashi Yasuhiko Kojima 《Phytotherapy research : PTR》1993,7(3):227-230
The inhibitory effects of glycoproteins separated from a hot water extract of corn silk (U-CSE) on the formation of IgE antibodies after primarily and secondarily challenged responses with dinitrophenyl (DNP)-ovalbumin (OVA) antigen in mice were investigated using the passive cutaneous anaphylaxis (PCA) test. When U-CSE was given intranasally or intraperitoneally the day before primary immunization, IgE antibody production was strongly inhibited. Furthermore, it was found that new formation of IgE antibodies was readily inhibited by U-CSE administration in mice with high levels of IgE after primary immunization. It was also found that U-CSE markedly suppressed IgE antibody formation in secondarily challenged responses with the antigen. U-CSE may be clinically applicable to type I allergic diseases. 相似文献
18.
In a patient who had undergone construction of a continent ileal pouch we successfully repaired an incontinent ileal tube by infolding it in an imbricated portion of the ileal pouch wall. For 2 years postoperatively the patient has been urine continent and has catheterized the pouch easily. We believe this infolding technique is useful for reconstructing the continent mechanism in patients with incompetent ileal valves. 相似文献
19.
Tsuneo Takebayashi Hiroyuki Obata Yasuhiko Minaki Masatoshi Sekine Kenshi Imoto Kazutoshi Yokogushi Toshihiko Yamashita 《Journal of orthopaedic science》2006,11(3):259-263
Background Cat cry syndrome is an autosomal disease accompanying abnormal deletion of chromosome 5 and occurs in only 1 of 50,000 neonates.
Scoliosis has been reported as a skeletal complication in cat cry syndrome. The characteristics and causes of scoliosis in
this rare syndrome are unknown. The purpose of this study was to present the characteristics of scoliosis in cat cry syndrome
and to speculate on its causative mechanisms.
Methods We report on 11 cases (5 boys and 6 girls) of cat cry syndrome. Detailed investigations of scoliosis, as well as physical
and imaging examinations, were performed to characterize scoliosis and its causes. Average age at initial diagnosis of scoliosis
was 4.3 years, and average age at final examination was 11.8 years.
Results The incidence of scoliosis was as high as 73% (8/11). Most cases show a single right thoracic curve. Of the 8 patients with
scoliosis, 3 patients who had increased muscular tone showed marked progression of scoliosis with growth.
Conclusions Muscular hypertonia may play a key role in the progression of scoliosis in cat cry syndrome. 相似文献
20.