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11.
Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells. 总被引:1,自引:0,他引:1
Franck Atienzar Helga Gerets Simon Dufrane Karen Tilmant Miranda Cornet Stephane Dhalluin Bernard Ruty Geoffrey Rose Michael Canning 《Toxicological sciences》2007,96(1):101-114
Phospholipidosis (PLD) is characterized by an intracellular accumulation of phospholipids in lysosomes and the concurrent development of concentric lamellar bodies. Recently, H. Sawada et al. (2005, Toxicol. Sci. 83, 282-292) identified 17 genes as potential biomarkers of PLD in HepG2 cells. The present study was undertaken to determine if this set of genes measured by quantitative PCR could be validated in the same cell line. The objective was also to investigate the dose-response relationship to further validate the assay and to select the concentrations to use for screening activities. In a first experiment (one concentration tested), out of the 17 genes, the best gene biomarkers of PLD (i.e., 11 genes) were selected for practical screening reasons. Based on these genes, 91.6% (i.e., 11 of 12) of the compounds known to induce PLD were identified as positive and all the negative compounds (i.e., five of five) were also confirmed. When the data obtained in the first experiment were compared to the data by Sawada et al., (2005) the coefficient of correlation calculated was slightly higher than 75%. In the second experiment (26 compounds [all 17 compounds from the first experiment plus 9 other compounds] tested at a minimum of three concentrations), 93.3% (14/15) of the compounds known to induce PLD were identified as such and all the negative controls (six compounds) were also confirmed. Three compounds likely to induce PLD were identified as positive in our assay. Finally, two compounds for which no data are available were also tested. When both experiments 1 and 2 were compared, the coefficient of correlation for 16 compounds tested at the same concentrations reached 87.7%. In conclusion, the present study further confirms the utility of gene expression in HepG2 cells to identify a potential to induce PLD. Finally, based on the data presented, researchers are encouraged to use a range of minimum three concentrations (e.g., 12.5, 25, and 50 microM) to screen for PLD in the human HepG2 cell line. 相似文献
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13.
Müllerian duct regression is first apparent in male pouch young of the tammar wallaby (Macropus eugenii) 6–7 days after birth and, as in eutherian mammals, is characterised by a condensation of the periductal mesenchyme into
a whorl around the ductal epithelial cells. A decrease in the density of the extracellular matrix was observed in the region
of the whorl. In contrast to eutherian mammals no changes were observed in the mean outer diameter of the Müllerian duct during
the early stages of regression. The time at which these mesenchymal changes occur corresponds to the period of Müllerian inhibiting
substance secretion in the postnatal tammar testis.
Accepted: 25 February 1997 相似文献
14.
Brigden Geoffrey Zanelli Giussepe Lahiri Avijit Raftery Edward 《European journal of nuclear medicine and molecular imaging》1990,16(11):795-799
A new, single bolus method of in vivo blood pool imaging using a technetium Tc99m phosphine isocyanide complex (DEPIC) which binds to pre-albumin was evaluated in volunteers (n=4) and patients (n=20). DEPIC was assessed for its safety and possible drug interactions. Its duration of action and quality of ventriculography were compared with imaging using standard in vivo red cell labelling (PYP) during two 3-h scanning periods 1 week apart. DEPIC had a mean plasma halflife of 3.3 h. The count rate over the left ventricle was initially 42% higher with DEPIC than with PYP. However, removal of DEPIC by the liver resulted in equivalent count rates by 1 h, and by 3 h PYP count rates were 22% higher than DEPIC. Immediately post injection mean (SD) difference in the left ventricular ejection fraction between the two methods was 2.4% (7.7%). Satisfactory DEPIC scans were obtained up to 2 h post injection, but by 3 h there was a mean difference of 13% (11.3%). DEPIC was found to be a safe alternative to red all labelling for blood pool angiography, suitable for routine work. The single bolus methodology and high initial count rates offer improved efficiency and a capability for truly emergency scanning. 相似文献
15.
Serum and Cerebrospinal Fluid Pharmacokinetics of Intravenous and Oral Lamivudine in Human Immunodeficiency Virus-Infected Children 总被引:3,自引:3,他引:0 下载免费PDF全文
Brigitta U. Mueller Linda L. Lewis Geoffrey J. Yuen Maureen Farley Amy Keller Joseph A. Church Jonathan C. Goldsmith David J. Venzon Marc Rubin Philip A. Pizzo Frank M. Balis 《Antimicrobial agents and chemotherapy》1998,42(12):3187-3192
We studied the pharmacokinetics of intravenously and orally administered lamivudine at six dose levels ranging from 0.5 to 10 mg/kg of body weight in 52 children with human immunodeficiency virus infection. A two-compartment model with first-order elimination from the central compartment was simultaneously fitted to the serum drug concentration-time data obtained after intravenous and oral administration. The maximal concentration at the end of the 1-h intravenous infusion and the area under the concentration-time curve after oral and intravenous administration increased proportionally with the dose. The mean clearance of lamivudine (± standard deviation) in the children was 0.53 ± 0.19 liter/kg/h (229 ± 77 ml/min/m2 of body surface area), and the mean half-lives at the distribution and elimination phases were 0.23 ± 0.18 and 2.2 ± 2.1 h, respectively. Clearance was age dependent when normalized to body weight but age independent when normalized to body surface area. Lamivudine was rapidly absorbed after oral administration, and 66% ± 25% of the oral dose was absorbed. Serum lamivudine concentrations were maintained above 1 μM for ≥8 h of 24 h on the twice daily oral dosing schedule with doses of ≥2 mg/kg. The cerebrospinal fluid drug concentration measured 2 to 4 h after the dose was 12% (range, 0 to 46%) of the simultaneously measured serum drug concentration. A limited-sampling strategy was developed to estimate the area under the concentration-time curve for concentrations in serum at 2 and 6 h. 相似文献
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17.
Geoffrey Thiele Molly Bicak Helen Grierson Patrick Lai David Purtilo 《Journal of immunological methods》1987,100(1-2):249-259
An enzyme-linked immunosorbent assay (ELISA) was used to measured IgG antiboody titers againt a synthetic peptide whose sequence was derived from the glycine-alanine repeating region of Epstein-Barr virus nuclear associated antigen 1 (EBNA-1). Antibody titers were determined in sera from 15 normal subjects, sera from 21 normal male siblings of X-linked lymphoproliferative syndrome (XLP) patients, from 20 XLP patients comprising a total of 42 samples, and ten samples before and ten samples after gamma-globulin therapy in ten patients with XLP. Data analysis demonstrated that while there are differences between the ELISA and ACIF, they appear to measure a similar response as demonstrated by their correlation coefficient (0.77) and the GMT to EBNA observed by both methods. No cross-reactivity of cytomegalovirus antibodies to the EBNA-1 peptide was observed by immunobv using adsorption against AD-169 infected MRC-5 cells.. However, non-specific binding was observed if samples were not pre-incubated in a 10% goat serum PBS-Tween 20 solution. This pre-treatment removed the non-specific binding that falsely elevated GMT in approximately 15% of both normal and XLP samples in ELISA. The ELISA system appears to be a sensitive, reproducible and objective test that may be useful for assessing the antibody responses of patients to the EBNA-1 protein. 相似文献
18.
19.
S C Gross H K Watson J W Strickland A K Palmer L H Brenner J Fatti 《The Journal of hand surgery》1989,14(1):95-102
Until recently the problem of painful, symptomatic arthritis of the wrist secondary to congenitally incomplete separation of carpal bones has been infrequently recognized. Five patients with either excessive stress loading or trauma had eight symptomatic wrists with congenitally incomplete separation of the triquetral-lunate joint. Three of these patients had bilateral symptoms. Six of the wrists had been treated by a limited wrist arthrodesis of the triquetral-lunate joint resulting in asymptomatic wrists and improved range of motion. It appears that patients with this congenital condition poorly tolerate stress loading or trauma secondary to deficient intra-articular cartilage formation resulting in a clinical and anatomic state similar to degenerative arthritis. We suggest a limited wrist arthrodesis as definitive treatment for symptomatic congenitally incomplete separation of the triquetral-lunate joint, with possible application in incomplete separation of the other intercarpal joints. 相似文献
20.