全文获取类型
收费全文 | 7916篇 |
免费 | 427篇 |
国内免费 | 73篇 |
专业分类
耳鼻咽喉 | 53篇 |
儿科学 | 173篇 |
妇产科学 | 643篇 |
基础医学 | 892篇 |
口腔科学 | 120篇 |
临床医学 | 894篇 |
内科学 | 1631篇 |
皮肤病学 | 78篇 |
神经病学 | 522篇 |
特种医学 | 240篇 |
外科学 | 1058篇 |
综合类 | 176篇 |
预防医学 | 401篇 |
眼科学 | 72篇 |
药学 | 584篇 |
中国医学 | 114篇 |
肿瘤学 | 765篇 |
出版年
2023年 | 38篇 |
2022年 | 95篇 |
2021年 | 174篇 |
2020年 | 92篇 |
2019年 | 145篇 |
2018年 | 244篇 |
2017年 | 166篇 |
2016年 | 155篇 |
2015年 | 206篇 |
2014年 | 241篇 |
2013年 | 378篇 |
2012年 | 568篇 |
2011年 | 578篇 |
2010年 | 370篇 |
2009年 | 309篇 |
2008年 | 492篇 |
2007年 | 538篇 |
2006年 | 536篇 |
2005年 | 435篇 |
2004年 | 378篇 |
2003年 | 317篇 |
2002年 | 310篇 |
2001年 | 262篇 |
2000年 | 271篇 |
1999年 | 201篇 |
1998年 | 53篇 |
1997年 | 55篇 |
1996年 | 57篇 |
1995年 | 31篇 |
1994年 | 44篇 |
1993年 | 25篇 |
1992年 | 128篇 |
1991年 | 91篇 |
1990年 | 67篇 |
1989年 | 42篇 |
1988年 | 46篇 |
1987年 | 44篇 |
1986年 | 44篇 |
1985年 | 27篇 |
1984年 | 34篇 |
1983年 | 11篇 |
1982年 | 7篇 |
1981年 | 13篇 |
1980年 | 6篇 |
1979年 | 15篇 |
1977年 | 6篇 |
1976年 | 5篇 |
1973年 | 7篇 |
1972年 | 7篇 |
1971年 | 10篇 |
排序方式: 共有8416条查询结果,搜索用时 15 毫秒
61.
Characteristics of optic disc changes in Taiwanese patients with primary angle-closure glaucoma. 总被引:1,自引:0,他引:1
Chang-Hao Yang Por-Tying Hung Luke L-K Lin Jui-Wen Hsieh Tsing-Hong Wang I Jong Wang 《台湾医志》2003,102(3):183-188
BACKGROUND AND PURPOSE: Primary angle-closure glaucoma (PACG) is the predominant form of glaucoma among Asians. Although numerous studies have been done to describe the characteristic optic disc changes in patients with primary open angle glaucoma (POAG) which is the predominant form of glaucoma among Western populations, few studies have evaluated the optic disc changes in patients with PACG. The aim of this study was to elucidate the characteristic intrapapillary and parapapillary disc changes in PACG in a cross-sectional study and to develop a practical approach to the detection of glaucomatous optic disc changes in PACG by ophthalmoscopic examination. METHODS: A total of 103 eyes in 103 PACG patients were studied. Forty one eyes of 41 age- and sex-matched healthy subjects served as controls. Three glaucoma-trained subspecialists examined stereophotographs of optic discs to evaluate the intrapapillary and parapapillary changes. The differences in PACG and control group eyes were compared. RESULTS: Concentric steep enlargement of the optic disc was found in 99 PACG eyes (96%). Local notching was noted in only 3 eyes, and vertically oval-shaped cupping of the optic disc in only 1 eye. Disc hemorrhage was not detected in any eye. Parapapillary atrophy of the alpha zone involving both temporal and nasal side of the optic disc and parapapillary atrophy of beta zone were significantly more frequent in the PACG group. The presence of an alpha zone or a beta zone simultaneously involving both the temporal and nasal side of the optic disc was associated with more severe optic nerve head damage. CONCLUSIONS: The intrapapillary change in the PACG group eyes reflected the development of cupping in PACG patients with small and compact optic discs. The parapapillary atrophy paralleled the intrapapillary optic disc cupping in eyes of the PACG group. 相似文献
62.
Asha Padar Ubaradka G Sathyanarayana Makoto Suzuki Riichiroh Maruyama Jer-Tsong Hsieh Eugene P Frenkel John D Minna Adi F Gazdar 《Clinical cancer research》2003,9(13):4730-4734
PURPOSE: Loss or abnormal expression of Cyclin D2, a crucial cell cycle-regulatory gene, has been described in human cancers; however, data for prostate tumors are lacking. We investigated the epigenetic silencing of Cyclin D2 gene in prostate cancers and correlated the data with clinicopathological features. EXPERIMENTAL DESIGN: Cyclin D2 promoter methylation was analyzed in 101 prostate cancer samples by methylation-specific PCR. In addition, we analyzed 32 nonmalignant prostate tissue samples, which included 24 samples of benign disease, benign prostatic hypertrophy, or prostatitis and 7 normal tissues adjacent to cancer. The methylation status of Cyclin D2 was correlated with the methylation of nine other tumor suppressor genes published previously from our laboratory on the same set of samples (R. Maruyama et al., Clin. Cancer Res., 8: 514-519, 2002). The methylation index was determined as a reflection of the methylated fraction of the genes examined. RESULTS: The frequency of methylation of Cyclin D2 promoter was significantly higher in prostate cancers (32%) than in nonmalignant prostate tissues (6%; P = 0.004), and it was not age related. Aberrant methylation was present at insignificant levels in peripheral blood lymphocytes (8%). We also compared methylation of cyclin D2 with methylation of nine tumor suppressor genes [published previously from our laboratory (R. Maruyama et al., Clin. Cancer Res., 8: 514-519, 2002)] studied in the same set of samples. The concordances between methylation of Cyclin D2 and the methylation of RARbeta, GSTP1, CDH13, RASSF1A, and APC were statistically significant, whereas methylation of P16, DAPK, FHIT, and CDH1 were not significant. The differences in methylation index between malignant and nonmalignant tissues for all 10 genes were statistically significant (P < 0.0001). Among clinicopathological correlations, the high Gleason score group had significantly greater methylation frequency of Cyclin D2 (42%; P = 0.004). Although the high preoperative serum prostate-specific antigen (PSA) group did not have significantly greater methylation frequency, methylation of Cyclin D2 had higher mean PSA value. Also, the prostate cancers in the high Gleason score group had high mean values of PSA. CONCLUSIONS: Our results indicate that methylation of Cyclin D2 in prostate cancers correlates with clinicopathological features of poor prognosis. These findings are of biological and potential clinical importance. 相似文献
63.
Pentoxifylline inhibits human peritoneal mesothelial cell growth and collagen synthesis: effects on TGF-beta 总被引:6,自引:0,他引:6
BACKGROUND: Prevention or treatment of peritoneal fibrosing syndrome has become an important issue in patients on continuous ambulatory peritoneal dialysis (CAPD). Recent evidence has suggested that mesothelial stem cell proliferation and matrix over-production predispose the development of peritoneal fibrosis. We investigated whether pentoxifylline (PTX) affects human peritoneal mesothelial cell (HPMC) growth and collagen synthesis. METHODS: HPMC was cultured from human omentum by an enzymic disaggregation method. Cell proliferation was assayed using a methyltetrazolium uptake method. Cell cycle analysis was performed by flow cytometry. Collagen synthesis was measured by 3H-proline incorporation into pepsin-resistant, salt-precipitated collagen. Prostaglandins and cAMP were determined by enzyme immunoassay. Northern blot analysis was used to determine mRNA expression. RESULTS: Our data show that PTX inhibited serum-stimulated HPMC growth and collagen synthesis in a dose-dependent manner. Cell cycle analysis showed that PTX arrested the HPMCs in the G1 phase. PTX decreased the procollagen alpha1 (I) mRNA expression either stimulated by serum or transforming growth factor-beta (TGF-beta). PTX did not alter prostaglandins synthesis but dose-dependently increased intracellular cAMP level. PTX, the same as 3-isobutyl-l-methylxanthine, could potentiate prostaglandin E1 (PGE1) increased cAMP levels of HPMC. The antimitogenic and antifibrogenic effects of PTX on HPMC were reversed by N-[2]-((p-Bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide (H-89). Therefore, the mechanism of these effects may be due to the phospodiesterase inhibitory property of PTX. CONCLUSIONS: These data suggest that PTX may have a role in treating peritoneal fibrosing syndrome. 相似文献
64.
The authors investigated the long-term stability of risk factors in predicting the presence of active trachoma and severe inflammatory trachoma in 176 children in Kongwa, Tanzania, who were aged 1 and 2 years in 1989 and were available for follow-up in 1995. Familial cattle ownership, living more than 2 hours away from a water source, and facial cleanliness at both time points were associated with the presence of active trachoma at both time points (odds ratio (OR) = 2.58, 95% confidence interval (CI): 1.15, 5.79; OR = 3.07, 95% CI: 1.23, 7.64; and OR = 0.52, 95% CI: 0.26, 1.03, respectively). An association of familial cattle ownership with facial cleanliness and water accessibility was observed. Having a clean face at both time points was associated with lower odds of active trachoma at both time points for children in non-cattle-herding families (OR = 0.40, 95% CI: 0.18, 0.87). Living more than 2 hours away from a water source at both time points increased the odds of active trachoma at both time points in children of cattle-herding families (OR = 8.00, 95% CI: 1.99, 32.10). Noticeably, severe inflammatory trachoma at baseline predicted mortality in children from villages in which trachoma was less common (OR = 3.75, 95% CI: 1.09, 12.98). The results suggest that risk factor reduction could diminish persistent disease. 相似文献
65.
66.
67.
Wang WS; Hsieh RK; Chiou TJ; Liu JH; Fan FS; Yen CC; Tung SL; Chen PM 《Japanese journal of clinical oncology》1998,28(9):551-554
A 54-year-old man was treated with weekly 24-h infusion of high-dose
5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon
cancer. At first, he tolerated the treatment well and no significant
toxicity was identified. After a total of eight courses of treatment, a
stable disease was observed, but mild shortness of breath was found on
occasion. The patient had no previous history of cardiac disease and the
heart performance assessed by left ventricular ejection fraction before
treatment was normal. Unfortunately, acute pulmonary edema with lethal
cardiogenic shock occurred during the ninth course of treatment, in spite
of intensive medical treatment. The chest X-ray showed extreme
cardiomegaly. Repeated assessment of his heart function by echocardiogram
and ventricular ejection fraction revealed a very poor cardiac performance.
Toxic cardiogenic shock during weekly 24-h infusion of high-dose
5-fluorouracil and leucovorin is extremely rare. To the best of our
knowledge, no case has been reported in the English literature. We report a
case and the relevant literature about the incidence, clinical picture and
possible pathophysiology on 5-fluorouracil-related cardioxicity is
reviewed.
相似文献
68.
Yao-Yuan Hsieh Chi-Chen Chang Chien-Chung Lee Horng-Der Tsai Cheng-Chieh Lin Chang-Hai Tsai 《Archives of gynecology and obstetrics》1998,261(3):163-166
We present a report on a case of conjoined twin/s (cephalothoracopagus janiceps monosymmetros) diagnosed by ultrasonography
and X-ray at 27 weeks' gestation.
Accepted: 29 December 1997 相似文献
69.
Teresa Pekol J Scott Daniels Jason Labutti Ian Parsons Darrell Nix Elizabeth Baronas Frank Hsieh Liang-Shang Gan Gerald Miwa 《Drug metabolism and disposition》2005,33(6):771-777
Bortezomib [N-(2,3-pyrazine)carbonyl-L-phenylalanine-L-leucine boronic acid] is a potent first-in-class dipeptidyl boronic acid proteasome inhibitor that was approved in May 2003 in the United States for the treatment of patients with relapsed multiple myeloma where the disease is refractory to conventional lines of therapy. Bortezomib binds the proteasome via the boronic acid moiety, and therefore, the presence of this moiety is necessary to achieve proteasome inhibition. Metabolites in plasma obtained from patients receiving a single intravenous dose of bortezomib were identified and characterized by liquid chromatography/mass spectrometry (LC/MS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS). Metabolite standards that were synthesized and characterized by LC/MS/MS and high field nuclear magnetic resonance spectroscopy (NMR) were used to confirm metabolite structures. The principal biotransformation pathway observed was oxidative deboronation, most notably to a pair of diastereomeric carbinolamide metabolites. Further metabolism of the leucine and phenylalanine moieties produced tertiary hydroxylated metabolites and a metabolite hydroxylated at the benzylic position, respectively. Conversion of the carbinolamides to the corresponding amide and carboxylic acid was also observed. Human liver microsomes adequately modeled the in vivo metabolism of bortezomib, as the principal circulating metabolites were observed in vitro. Using cDNA-expressed cytochrome P450 isoenzymes, it was determined that several isoforms contributed to the metabolism of bortezomib, including CYP3A4, CYP2C19, CYP1A2, CYP2D6, and CYP2C9. The development of bortezomib has provided an opportunity to describe the metabolism of a novel boronic acid pharmacophore. 相似文献
70.
To investigate synaptic mechanisms underlying information processing in auditory cortex, we examined cholinergic modulation of synaptic transmission in a novel slice preparation containing thalamocortical and intracortical inputs to mouse auditory cortex. Extracellular and intracellular recordings were made in cortical layer IV while alternately stimulating thalamocortical afferents (via medial geniculate or downstream subcortical stimulation) and intracortical afferents. Either subcortical or intracortical stimulation elicited a fast, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-sensitive, monosynaptic EPSP followed by long-duration, polysynaptic activity. The cholinergic agonist carbachol suppressed each of the synaptic potentials to different degrees. At low concentrations (5 μM) carbachol strongly reduced (>60%) the polysynaptic slow potentials for both pathways but did not affect the monosynaptic fast potentials. At higher doses (10–50 μM), carbachol also reduced the fast potentials, but reduced the intracortically-elicited fast potential significantly more than the thalamocortically-elicited fast potential, which at times was actually enhanced. Atropine (0.5 μM) blocked the effects of carbachol, indicating muscarinic receptor involvement. We conclude that muscarinic modulation can strongly suppress intracortical synaptic activity while exerting less suppression, or actually enhancing, thalamocortical inputs. Such differential actions imply that auditory information processing may favor sensory information relayed through the thalamus over ongoing cortical activity during periods of increased acetylcholine (ACh) release. 相似文献