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31.
Cyclin‐Dependent Kinase Inhibitor‐1‐Deficient Mice are Susceptible to Osteoarthritis Associated with Enhanced Inflammation 下载免费PDF全文
Shinsuke Kihara Shinya Hayashi Shingo Hashimoto Noriyuki Kanzaki Koji Takayama Tomoyuki Matsumoto Nobuaki Chinzei Kenjiro Iwasa Masahiko Haneda Kazuhiro Takeuchi Kotaro Nishida Ryosuke Kuroda 《Journal of bone and mineral research》2017,32(5):991-1001
Osteoarthritis (OA) is a multifactorial disease, and recent data suggested that cell cycle–related proteins play a role in OA pathology. Cyclin‐dependent kinase (CDK) inhibitor 1 (p21) regulates activation of other CDKs, and recently, we reported that p21 deficiency induced susceptibility to OA induced by destabilization of the medial meniscus (DMM) surgery through STAT3‐signaling activation. However, the mechanisms associated with why p21 deficiency led to susceptibility to OA by the STAT3 pathway remain unknown. Therefore, we focused on joint inflammation to determine the mechanisms associated with p21 function during in vitro and in vivo OA progression. p21‐knockout (p21?/?) mice were used to develop an in vivo OA model, and C57BL/6 (p21+/+) mice with the same background as the p21?/? mice were used as controls. Morphogenic changes were measured using micro‐CT, IL‐1β serum levels were detected by ELISA, and histological or immunohistological analyses were performed. Our results indicated that p21‐deficient DMM‐model mice exhibited significant subchondral bone destruction and cartilage degradation compared with wild‐type mice. Immunohistochemistry results revealed p21?/? mice susceptibility to OA changes accompanied by macrophage infiltration and enhanced MMP‐3 and MMP‐13 expression through IL‐1β‐induced NF‐κB signaling. p21?/? mice also showed subchondral bone destruction according to micro‐CT analysis, and cathepsin K staining revealed increased numbers of osteoclasts. Furthermore, p21?/? mice displayed increased serum IL‐1β levels, and isolated chondrocytes from p21?/? mice indicated elevated MMP‐3 and MMP‐13 expression with phosphorylation of IκB kinase complex in response to IL‐1β stimulation, whereas treatment with a specific p‐IκB kinase inhibitor attenuated MMP‐3 and MMP‐13 expression. Our results indicated that p21‐deficient DMM mice were susceptible to alterations in OA phenotype, including enhanced osteoclast expression, macrophage infiltration, and MMP expression through IL‐1β‐induced NF‐κB signaling, suggesting that p21 regulation may constitute a possible therapeutic strategy for OA treatment. © 2017 American Society for Bone and Mineral Research. 相似文献
32.
Satoru Motokawa Takafumi Torigoshi Yumi Maeda Kazushige Maeda Yuka Jiuchi Takayuki Yamaguchi Shinsuke Someya Hiroyuki Shindo Kiyoshi Migita 《BMC musculoskeletal disorders》2011,12(1):22
Background
Heparin-induced thrombocytopenia (HIT) is a thromboembolic complication that can occur with unfractionated heparin (UFH) or low molecular weight heparin (LMWH). Our objective was to determine and compare the incidence of IgG-class HIT antibodies in patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) with different antithrombotic prophylaxis therapies and their contributions to the occurrence of venous thromboembolism (VTE). 相似文献33.
34.
Watabe N Nishino A Arai H Nishimura S Suzuki S Uenohara H Sakurai Y Suzuki H 《No shinkei geka. Neurological surgery》2005,33(9):925-929
We reported an autopsy case of Down's syndrome with moyamoya syndrome. A 30-year-old male with Down's syndrome suffered from a cerebral infarction and died of brain herniation. Cerebral angiography showed vascular abnormalities that were the same as moyamoya disease. Pathological findings revealed multiple stenosis of main trunk of the cerebral arteries. Pathologically, the stenosed vessels showed eccentric intimal thickness with cholesterin deposit, unlike moyamoya disease. There are only two previous reports of autopsied cases of Down's syndrome with moyamoya syndrome. We postulate that a protein encoded on chromosome 21 may be related to the pathogenesis of Down's syndrome with moyamoya syndrome. 相似文献
35.
Successful treatment of a patient with penetrating injury of the esophagus and brachiocephalic artery due to migration of Kirschner wires. 总被引:2,自引:0,他引:2
Shinsuke Wada Tsuyoshi Noguchi Tsuyoshi Hashimoto Yuzo Uchida Katsunobu Kawahara 《Annals of thoracic and cardiovascular surgery》2005,11(5):313-315
Pins and wires offer the simplest and most effective tools for managing bone fractures and dislocations. Migration of these devices within the chest is rare, but can cause serious problems. The spontaneous migration of Kirschner wires from the right clavicle to the mediastinum resulted in penetrating injury of the esophagus and pseudo-aneurysm of the brachiocephalic artery in an 84-year-old patient. Two Kirschner wires were removed via a vertical incision on the right shoulder without thoracotomy and the brachiocephalic artery was replaced with a Dacron graft. 相似文献
36.
Noguchi T Oue N Wada S Sentani K Sakamoto N Kikuchi A Yasui W 《Annals of surgical oncology》2009,16(5):1390-1396
Background The human homologue of Drosophila prune (PRUNE, which encodes h-prune) protein interacts with glycogen synthase kinase 3 and promotes cell motility. The aim
of our study was to investigate the impact of immunohistochemically detected h-prune expression on the survival of patients
with esophageal squamous cell carcinoma (ESCC).
Methods Immunohistochemical staining of h-prune was performed for 205 surgically resected specimens of ESCC.
Results In total, 43 (21%) of 205 ESCC cases were positive for h-prune. h-prune-positive ESCC cases showed a more-advanced T stage
(P < 0.0001), N stage (P < 0.0001), and tumor stage (P < 0.0001) than h-prune-negative ESCC cases. In the group of 116 stage II and III ESCC cases, recurrence of ESCC was frequently
found in h-prune-positive cases. In patients with lung recurrence, the tumors were more likely to be h-prune positive than
h-prune negative. Univariate analysis revealed that T stage (P < 0.0001), N stage (P < 0.0001), tumor stage (P < 0.0001), and h-prune staining (P < 0.0001) were significant prognostic factors for survival. Multivariate analysis indicated that N stage (P = 0.0182) and h-prune staining (P < 0.0001) were independent predictors for survival.
Conclusions These results indicate that immunostaining of h-prune is useful to identify patients at high risk for recurrence or poor prognosis
associated with ESCC. 相似文献
37.
Tomoki Makino MD Makoto Yamasaki MD Ichiro Takemasa MD Atsushi Takeno MD Yurika Nakamura PhD Hiroshi Miyata MD Shuji Takiguchi MD Yoshiyuki Fujiwara MD Nariaki Matsuura MD Masaki Mori MD Yuichiro Doki MD 《Annals of surgical oncology》2009,16(7):2058-2064
Background and Objectives Dickkopf-1 (DKK1) is the inhibitor of the canonical Wnt signaling pathway, however it is highly transactivated in various
cancers, suggesting the presence of unknown mechanism. Its implication in human esophageal squamous cell carcinoma (ESCC)
has not been sufficiently investigated.
Patients and Methods We evaluated DKK1 protein expression in resected specimens from 170 patients with ESCC by immunohistochemistry. Tumors were
categorized as positive or negative for DKK1. The relationships between DKK1 expression in ESCC and various clinicopathological
parameters and prognosis (disease-free survival; DFS) were analyzed separately.
Results Immunohistochemically, 72 (42.4%) tumors were DKK1 positive while no significant staining was observed in the normal squamous
epithelium except for few basal cells. There was no significant relationship between DKK1 expression in ESCC and any of the
clinicopathological parameters tested in this study. Patients with DKK1-positive tumors had poorer DFS than those with negative
ESCC (5-year DFS; 31.5% versus 53.6%, P = 0.0062). Univariate analysis showed a significant relationship between pT [hazard ratio (HR) = 2.944, 95% confidence interval
(CI) = 1.713–5.059, P < 0.0001], number of pN (HR = 2.836, 95% CI = 1.866–4.309, P < 0.0001), lymphatic invasion (HR = 2.892, 95% CI = 1.336–6.262, P = 0.0070), and DKK1 expression (HR = 1.763, 95% CI = 1.167–2.663, P = 0.0071) and DFS. Multivariate analysis including the above four parameters identified pT (HR = 2.053, 95% CI = 1.157–3.645,
P = 0.0140), pN number (HR = 2.107, 95% CI = 1.362–3.260, P = 0.0008), and DKK1 expression (HR = 1.813, 95% CI = 1.195–2.751, P = 0.0052) as independent and significant prognostic factors for DFS.
Conclusion Our data suggest the usefulness of DKK1 as a novel predictor of poor prognosis of patients with ESCC after curative resection
and also as a therapeutic target for future tailored therapies against ESCC. 相似文献
38.
Yasuo Kokubo Hisashi Oki Daisuke Sugita Kohei Negoro Kenichi Takeno Tsuyoshi Miyazaki Hideaki Nakajima 《European journal of orthopaedic surgery & traumatology : orthopedie traumatologie》2016,26(4):407-413
The aim of the present study was to analyze the clinical and radiographic outcomes and Kaplan–Meier survivorship of patients who underwent revision surgeries of the acetabular cup that had sustained aseptic loosening. We reviewed 101 consecutive patients (120 hips; 10 men 11 hips; 91 women 109 hips; age at surgery 66 years; range 45–85) who underwent acetabular component revision surgery, at a follow-up period of 15.6 years (range 10–32). To evaluate the state of the acetabulum, acetabular bony defects were classified according to the AAOS classification based on intraoperative findings: type I (segmental deficiencies n = 24 hips), type II (cavity deficiency n = 48), type III (combined deficiency n = 46), and type IV (pelvic discontinuity n = 2). The Harris hip score improved from 42.5 ± 10.8 (mean ± SD) before surgery to 74.9 ± 14.6 points at follow-up. The survival rates of the acetabular revision surgery with cemented, cementless, and cemented cups plus reinforcement devices were 74, 66, and 82 %, respectively. The difference in the survival rate between the cemented and cementless group was marginal (p = 0.048 Gehan–Breslow–Wilcoxon, p = 0.061 log-rank), probably due to the early-stage failure cases in the cementless group. The cementless and reinforcement groups included nine early-stage failure cases. To prevent early-stage failure, we recommend the cementless cups for types I and II acetabular bone defects with adequate contact between host bone and acetabular component, and the cemented cup with or without reinforcement devices, together with restoration of bone stock by impaction or structured bone grafting, for cases lacking such contact. 相似文献
39.
40.
Junko?KishikawaEmail author Shinsuke?Kazama Koji?Oba Kiyoshi?Hasegawa Hiroyuki?Anzai Yuzo?Harada Hiroyuki?Abe Keisuke?Matsusaka Kumiko?Hongo Masaru?Oba Koji?Yasuda Kensuke?Otani Takeshi?Nishikawa Toshiaki?Tanaka Junichiro?Tanaka Tomomichi?Kiyomatsu Keisuke?Hata Kazushige?Kawai Hiroaki?Nozawa Hironori?Yamaguchi Soichiro?Ishihara Eiji?Sunami Tetsuo?Ushiku Joji?Kitayama Masashi?Fukayama Norihiro?Kokudo Toshiaki?Watanabe 《Annals of surgical oncology》2016,23(6):1916-1923