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961.
Several lines of evidence suggest that cholinergic deficits may contribute to the pathophysiology of psychiatric disorders as well as Alzheimer's disease. There is growing clinical evidence that galantamine, currently used for the treatment of Alzheimer's disease, may improve cognitive dysfunction and psychiatric illness in schizophrenia, major depression, bipolar disorder, and alcohol abuse. Since galantamine is a rather weak acetylcholinesterase inhibitor, but has additional allosteric potentiating effects at nicotinic receptors, it affects not only cholinergic transmission but also other neurotransmitter systems such as monoamines, glutamate, and γ-aminobutyric acid (GABA) through its allosteric mechanism. It is likely that these effects may result in more beneficial effects. To understand the underlying mechanism for the clinical effectiveness of galantamine, neuropharmacological studies have been performed in animal models of several psychiatric disorders. These studies suggest that not only the nicotinic receptor-modulating properties but also the muscarinic receptor activation contribute to the antipsychotic effect and improvement of cognitive dysfunction by galantamine. This review summaries the current status on the pharmacology of galantamine, focusing on its effect on neurotransmitter release and pharmacological studies in animal models of psychiatric disorders. 相似文献
962.
Thatcher SE Fultz ME Tanaka H Hagiwara H Zhang HL Zhang Y Hayakawa K Yoshiyama S Nakamura A Wang HH Katayama T Watanabe M Lin Y Wright GL Kohama K 《Journal of pharmacological sciences》2011,116(1):116-127
Previous work has suggested that in addition to its kinase activity, myosin light chain kinase (MLCK) exhibits non-kinase properties within its N-terminus that could influence cytoskeletal organization of smooth muscle cells (A. Nakamura et al. Biochem Biophys Res Commun. 2008;369:135-143). Myosin ATPase activity measurements indicate that the 26-41 peptide of MLCK significantly decreases ATPase activity as the concentration of this peptide increases. Sliding velocity of actin-filaments on myosin and stress responses in skinned smooth muscle tissue are also inhibited. Peptide-mediated uptake and the microinjection technique in cells indicate that the peptide was necessary for actin-filament stabilization. Fluorescence resonance energy transfer analysis indicated that in the presence of MLCK, α-actin but not β-actin remodeled during phorbol 12,13-dibutyrate (PDBu)-induced contractions. PDBu also induced podosomes in the cell. When MLCK expression was down-regulated by introduction of RNAi for MLCK by lentivirus vector into the cells, we failed to observe the podosome induction upon PDBu stimulation. Rescue experiments indicate that the non-kinase activity of MLCK plays an important role in maintaining actin stress fibers and in the PDBu-induced reorganization of actin-filaments in smooth muscle cells. 相似文献
963.
Takawa M Masuda K Kunizaki M Daigo Y Takagi K Iwai Y Cho HS Toyokawa G Yamane Y Maejima K Field HI Kobayashi T Akasu T Sugiyama M Tsuchiya E Atomi Y Ponder BA Nakamura Y Hamamoto R 《Cancer science》2011,102(7):1298-1305
The emphasis in anticancer drug discovery has always been on finding a drug with great antitumor potential but few side-effects. This can be achieved if the drug is specific for a molecular site found only in tumor cells. Here, we find the enhancer of zeste homolog 2 (EZH2) to be highly overexpressed in lung and other cancers, and show that EZH2 is integral to proliferation in cancer cells. Quantitative real-time PCR analysis revealed higher expression of EZH2 in clinical bladder cancer tissues than in corresponding non-neoplastic tissues (P < 0.0001), and we confirmed that a wide range of cancers also overexpress EZH2, using cDNA microarray analysis. Immunohistochemical analysis showed positive staining for EZH2 in 14 of 29 cases of bladder cancer, 135 of 292 cases of non-small-cell lung cancer (NSCLC), and 214 of 245 cases of colorectal cancer, whereas no significant staining was observed in various normal tissues. We found elevated expression of EZH2 to be associated with poor prognosis for patients with NSCLC (P = 0.0239). In lung and bladder cancer cells overexpressing EZH2, suppression of EZH2 using specific siRNAs inhibited incorporation of BrdU and resulted in significant suppression of cell growth, even though no significant effect was observed in the normal cell strain CCD-18Co, which has undetectable EZH2. Because EZH2 expression was scarcely detectable in all normal tissues we examined, EZH2 shows promise as a tumor-specific therapeutic target. Furthermore, as elevated levels of EZH2 are associated with poor prognosis of patients with NSCLC, its overexpression in resected specimens could prove a useful molecular marker, indicating the necessity for a more extensive follow-up in some lung cancer patients after surgical treatment. 相似文献
964.
Takuo Hara Kazuhiro Nishikawa Mitsuaki Sakatoku Koji Oba Junichi Sakamoto Kenji Omura 《Gastric cancer》2011,14(4):332-338
Background
Our previous phase I study provided evidence that weekly paclitaxel, cisplatin, and bolus 5-fluorouracil (weekly PCF) was effective and well tolerated in patients with advanced gastric cancer. This study was conducted to confirm the efficacy and toxicity of weekly PCF. 相似文献965.
Sakai K Miyahara T Tsutsumi K Kaneko T Fukushima M Tanaka Y Hongo K 《Brain tumor pathology》2011,28(2):151-156
We present a case of spontaneous regression of multicentric pilocytic astrocytoma with cerebrospinal fluid (CSF) dissemination
without neurofibromatosis type 1 (NF1) in an adult, the first such case reported. Magnetic resonance imaging (MRI) showed
multiple low signal intensity lesions on T1-weighted images and high signal intensity areas on T2-weighted images in the bilateral
thalamus, basal ganglia and midbrain. Contrast-enhanced MRI revealed that small, enhanced lesions were seen in the basal ganglia
and the pineal region. Neuroendoscopic biopsy and third ventriculostomy were performed. Intraoperative findings demonstrated
CSF dissemination. Histologically, the specimens showed pilocytic astrocytoma. Serial MRIs showed regression of the tumor
without any additional treatment. The clinical features of spontaneous regression of pilocytic astrocytoma are discussed. 相似文献
966.
Nakajima T Yasufuku K Suzuki M Hiroshima K Nakatani Y Fujisawa T Yoshino I 《Clinical lung cancer》2011,12(5):293-297
967.
Takayuki Honda Yoshihito Tsuzaki Keiko Mitaka Kazuhiro Fukasawa Yoshihiro Miyashita Kan Marino Akitoshi Saito Toshio Oyama Naohiko Inase 《Case reports in oncology》2011,4(2):350-357
A 45-year-old man complaining of cough, dyspnea, and difficulty in swallowing was referred to our hospital. Chest CT scan showed a mediastinal mass compressing the trachea. He was diagnosed with poorly differentiated lung carcinoma by percutaneous needle biopsy. Bronchoscopy and upper gastrointestinal endoscopy revealed a tracheoesophageal fistula (TEF). Long-lasting febrile neutropenia made it impossible to continue chemotherapy, but a course of radiotherapy (total 61 Gy) was completed. The next endoscopy revealed closure of the TEF. Chemoradiotherapy (CRT) has been reported to close TEF in esophageal cancer, but the risk of a CRT-induced worsening of the fistula has dissuaded physicians from using CRT to treat TEF in lung cancer patients. CRT may serve as a palliative treatment for TEF in lung cancer as well as esophageal cancer.Key words: Chemoradiotherapy, Lung carcinoma, Tracheoesophageal fistula 相似文献
968.
Zennami K Yoshikawa K Kondo E Nakamura K Upsilonamada Y De Velasco MA Tanaka M Uemura H Shimazui T Akaza H Saga S Ueda R Honda N 《Oncology reports》2011,26(2):327-333
Molecular targeting agents have become formidable anticancer weapons showing much promise against refractory tumors and functional peptides and are among the more desirable of these nanobio-tools. Intracellular delivery of multiple functional peptides forms the basis for a potent, non-invasive mode of delivery, providing distinctive therapeutic advantages. We examine the growth suppression efficiency of human renal cell carcinoma (RCC) by single-peptide targeting. We simultaneously introduced p16INK4a tumor suppressor peptides by Wr-T-mediated peptide delivery. Wr-T-mediated transport of p16INK4a functional peptide into 10 RCC lines, lacking expression of the p16INK4a molecule, reversed the specific loss of p16 function, thereby drastically inhibiting tumor growth in all but 3 lines by >95% within the first 96?h. In?vivo analysis using SK-RC-7 RCC xenografts in nude mice demonstrated tumor growth inhibition by the p16INK4a peptide alone, however, inoculation of Wr-T and the p16INK4a functional peptide mixture, via the heart resulted in complete tumor regression. Thus, restoration of tumor suppressor function with Wr-T peptide delivery represents a powerful approach, with mechanistic implications for the development of efficacious molecular targeting therapeutics against intractable RCC. 相似文献
969.
Kasai K Ushio A Kasai Y Sawara K Miyamoto Y Oikawa K Kuroda H Takikawa Y Suzuki K 《International journal of clinical oncology / Japan Society of Clinical Oncology》2011,16(3):221-229
Background
This study evaluated the efficacy of combined 5-fluorouracil (5-FU) and pegylated interferon (PEG-IFN) α-2b in patients with advanced hepatocellular carcinoma (HCC). 相似文献970.