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991.
Naito T Mino Y Otsuka A Ushiyama T Ozono S Kagawa Y Kawakami J 《Biological & pharmaceutical bulletin》2008,31(6):1292-1296
The aim of this study was to evaluate the plasma trough concentrations (C(0)) of mycophenolic acid (MPA) and its major metabolite MPA 7-O-glucuronide (MPAG) in metal cation (MC)(-) (non-treated) and MC(+) (co-treated) patients who received tacrolimus (Tac) or cyclosporine (CyA). Fifty-nine Japanese stable kidney transplant recipients receiving immunosuppressive regimens containing mycophenolate mofetil (MMF) and a calcineurin inhibitor (CNI) were included in this study. Seven in the 25 patients receiving Tac and 8 in the 34 patients receiving CyA were treated with concomitant MCs administration. Multiple regression analysis revealed that concomitant MCs and CyA administration influenced MPA C(0). Their standardized partial regression coefficients were -0.29 and -0.41, respectively. Stratified analysis based on CNI treatment revealed that MPA C(0) decreased significantly by 56% with concomitant MCs administration in Tac-treated patients. There was no significant difference in MPA C(0) between the MC(-) and MC(+) groups in CyA-treated patients. With respect to MPAG C(0), MC(+) group tended to be lower by 26% than MC(-) group in Tac-treated patients. There was no significant difference in MPAG C(0) between the MC(-) and MC(+) groups in CyA-treated patients. Concomitant MCs administration did not affect the C(0) ratio of MPAG to MPA in either Tac- or CyA-treated patients. In conclusion, MCs co-administration decrease MPA C(0) in patients receiving Tac and may cause lower MPA exposure. There are little pharmacokinetic interactions between MMF and concomitant MCs in CyA-treated patients. 相似文献
992.
Sakai A Okami K Onuki J Miyasaka M Furuya H Iida M 《The Tokai journal of experimental and clinical medicine》2008,33(3):105-109
The risk factors for wound complications after surgery for head and neck cancers at Tokai University Hospital were evaluated. The medical records of 71 head and neck cancer patients who underwent surgery between January 2000 and December 2002 were reviewed. The overall incidence of postoperative complications was 39.4%. Uni- and multivariate analyses of the risk factors leading to complications demonstrated that free flap use was significant. Further, we analyzed the relationship between radiotherapy and postoperative complications. There was no significant correlation between them.The prevention and treatment of postoperative complications were discussed. 相似文献
993.
Mino Y Naito T Matsushita T Kagawa Y Kawakami J 《Journal of pharmaceutical and biomedical analysis》2008,46(3):603-608
Therapeutic drug monitoring (TDM) of mycophenolic acid (MPA) following administration of mycophenolate mofetil (MMF) or the enteric-coated sodium salt of MPA formulations, seems beneficial because of the large intra- and inter-individual variability in MPA pharmacokinetics. MPA is an active component from these oral formulations and are further metabolised to inactive phenolic glucuronide (MPAG) and active acyl glucuronide (AcMPAG). This study aims to determine simultaneously these three metabolites of MMF using isocratic ion pair HPLC and to evaluate the short-term stability of AcMPAG in human plasma. Samples were prepared using solid phase extraction. Chromatographic separation was achieved over an RP column (TSKgel ODS-80Ts, 150 mm x 4.6 mm i.d., 5 microm particle size) with acetonitrile and 30 mM tetra-n-butylammonium bromide containing 5 mM ammonium acetate at pH 9.0 (33/67, v/v) as the mobile phase. The flow rate of the mobile phase was 1ml/min, and the wavelength of determination by UV detection was 250 nm (run time, 16 min). Calibration curves for MPA, MPAG and AcMPAG in human plasma were linear over a concentration range of 0.05-50, 0.1-400 and 0.08-8 microg/ml, respectively. Intra- and inter-assay R.S.D. were<6.5%. Extraction efficiencies were more than 85% for all analytes. Since AcMPAG was unstable in human plasma, plasma acidification was needed for the quantification of AcMPAG. Large interindividual variability was observed in the AcMPAG pharmacokinetics in the early period after renal transplantation. In conclusion, a simple, accurate and reproducible HPLC method to measure simultaneously these three MMF metabolites has been established. The method will be helpful in evaluating pharmacokinetics of MPA and its glucuronides. 相似文献
994.
Kamiie J Ohtsuki S Iwase R Ohmine K Katsukura Y Yanai K Sekine Y Uchida Y Ito S Terasaki T 《Pharmaceutical research》2008,25(6):1469-1483
Purpose To develop an absolute quantification method for membrane proteins, and to construct a quantitative atlas of membrane transporter
proteins in the blood–brain barrier, liver and kidney of mouse.
Methods Mouse tissues were digested with trypsin, and mixed with stable isotope labeled-peptide as a quantitative standard. The amounts
of transporter proteins were simultaneously determined by liquid chromatography–tandem mass spectrometer (LC/MS/MS).
Results The target proteins were digested in-silico, and target peptides for analysis were chosen on the basis of the selection criteria.
All of the peptides selected exhibited a detection limit of 10 fmol and linearity over at least two orders of magnitude in
the calibration curve for LC/MS/MS analysis. The method was applied to obtain the expression levels of 34 transporters in
liver, kidney and blood–brain barrier of mouse. The quantitative values of transporter proteins showed an excellent correlation
with the values obtained with existing methods using antibodies or binding molecules.
Conclusion A sensitive and simultaneous quantification method was developed for membrane proteins. By using this method, we constructed
a quantitative atlas of membrane transporter proteins at the blood–brain barrier, liver and kidney in mouse. This technology
is expected to have major implications for various fields of biomedical science. 相似文献
995.
Irie O Kosaka T Ehara T Yokokawa F Kanazawa T Hirao H Iwasaki A Sakaki J Teno N Hitomi Y Iwasaki G Fukaya H Nonomura K Tanabe K Koizumi S Uchiyama N Bevan SJ Malcangio M Gentry C Fox AJ Yaqoob M Culshaw AJ Allan Hallett 《Journal of medicinal chemistry》2008,51(18):5502-5505
Cathepsin S inhibitors are well-known to be an attractive target as immunological therapeutic agents. Recently, our gene expression analysis identified that cathepsin S inhibitors could also be effective for neuropathic pain. Herein, we describe the efficacy of selective cathepsin S inhibitors as antihyperalgesics in a model of neuropathic pain in rats after oral administration. 相似文献
996.
997.
998.
Arai J Okada S Yamaguchi-Shima N Shimizu T Sasaki T Yorimitsu M Wakiguchi H Yokotani K 《Clinical and experimental pharmacology & physiology》2008,35(8):965-970
1. The aim of the present study was to characterize the source of plasma catecholamines induced by centrally administered glucagon-like peptide-1 (GLP-1), with regard to brain prostanoids, in urethane-anaesthetized rats. 2. Glucagon-like peptide-1 and other compounds were administered intracerebroventricularly (i.c.v.) and blood samples were collected via a cannula inserted into the femoral artery. Catecholamines were extracted from plasma with activated alumina and were assayed electrochemically using high-performance liquid chromatography. 3. At 0.3, 1.0 and 3.0 nmol/animal, GLP-1 dose-dependently elevated plasma levels of noradrenaline and adrenaline and the 1.0 nmol GLP-1-induced response was dose-dependently reduced by 5 and 10 nmol/animal exendin (5-39), a selective GLP-1 receptor antagonist. The GLP-1-induced elevation of concentrations of both catecholamines was abolished by 1.2 micromol/animal indomethacin, an inhibitor of cyclo-oxygenase, whereas 1.2 micromol/animal baicalein, a lipoxygenase inhibitor, had no effect. 4. Both furegrelate (1.8 micromol/animal; an inhibitor of thromboxane A(2) synthase) and (+)S-145 (625 nmol/animal; a thromboxane A(2) receptor antagonist) attenuated the GLP-1-induced increases in plasma adrenaline concentrations, but had no effect on the increases in plasma noradrenaline. The GLP-1-induced increase in plasma adrenaline concentrations was abolished by acute bilateral adrenalectomy, but the procedure had no effect on increases in plasma noradrenaline. 5. These results suggest that, in rats, centrally administered GLP-1 induces the secretion of adrenaline from the adrenal medulla by brain thromboxane A(2)-mediated mechanisms, whereas the peptide evokes the release of noradrenaline from sympathetic nerves by brain prostanoids via mechanisms other than those mediated by thromboxane A(2). 相似文献
999.
Akiko Ioka Masami Inoue Akihiro Yoneda Tetsuro Nakamura Junichi Hara Yoshiko Hashii Naoki Sakata Kazumi Yamato Hideaki Tsukuma Keisei Kawa 《Journal of epidemiology / Japan Epidemiological Association》2016,26(4):179-184
Background
In 2004, the Japanese government halted the 6-month mass screening program for neuroblastoma. We investigated whether its cessation had led to an increase not only in mortality due to this disease but also in the incidence of advanced-stage disease among older children.Methods
Study subjects were neuroblastoma patients retrieved from the population-based Osaka Cancer Registry. Trends of incidence and mortality from neuroblastoma were analyzed by calendar year and birth cohort. Prognostic factors, including stage and v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) oncogene status, were compared before and after the cessation of mass screening.Results
Age-standardized incidence rates in 2005–2009 (the cessation period of mass screening; 11.1 per million) were similar to those in 1975–1979 (the pre-screening period; 8.6 per million). Age-standardized mortality rates tended to decrease from 1975–1979 (4.0 per million) to 2005–2009 (2.7 per million) in parallel with the improvement in survival. Analysis by birth cohort indicated that the mortality rates in 2004–2005 (after cessation) for children 0–4 years of age were lower than those in 1975–1979 (O:E ratio 0.25; 95% confidence interval, 0.03–0.90). For children 1–9 years of age, there was a not significant difference in the distribution of stage, MYCN oncogene status, and DNA ploidy between 1991–2003 (the mass screening period) and 2004–2008 (after cessation).Conclusions
The cessation of mass screening for neuroblastoma does not appear to have increased mortality due to this disease or incidence of advanced-stage disease among older children.Key words: neuroblastoma, cessation, screening, mortality, incidence 相似文献1000.
Shimamura Junichi Nishimura Takashi Mizuno Toshihide Takewa Yoshiaki Tsukiya Tomonori Inatomi Ayako Katagiri Nobumasa Ando Masahiko Umeki Akihide Akiyama Daichi Arakawa Mamoru Ono Minoru Tatsumi Eisuke 《Journal of artificial organs》2019,22(4):348-352
Journal of Artificial Organs - The purpose of this study was to observe and clarify the interventricular dysscynchrony caused by continuous-flow left ventricular assist device (CF-LVAD) support... 相似文献