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31.
Endothelin antagonist treatment for successful liver transplantation from non-heart-beating donors 总被引:2,自引:0,他引:2
Fukunaga K Takada Y Taniguchi H Mei G Seino KI Yuzawa K Otsuka M Todoroki T Goto K Fukao K 《Transplantation》1999,67(2):328-332
BACKGROUND: With the shortage of cadaveric donors, non-heart-beating donors (NHBDs) are a potential source of liver allografts. However, warm ischemic injury in NHBDs seriously affects the viability of graft liver. Endothelin (ET)-1 has been reported to be involved in the hepatic microcirculatory disturbances after ischemia-reperfusion. METHODS: In a porcine orthotopic liver transplantation model, changes in the serum and liver tissue ET-1 concentration were measured and the effects of an ET receptor antagonist, TAK-044, were evaluated. After cardiac arrest of the donors, liver allografts were subjected to 90 min of warm ischemia, flushed, and preserved for 4 hr at 4 degrees C. The pigs were divided into two groups: a control group (no drug treatment) and a drug-treated group, in which donors and recipients were treated with TAK-044 (10 mg/kg body, drip intravenous injection). Both groups had six donor/recipient pairs. RESULTS: -The ET-1 concentration in the hepatic venous blood increased after reperfusion of the graft in the control group recipients. ET-1 in the graft liver significantly increased during the cold preservation period. TAK-044 treatment significantly increased recipient 7-day survival rate. After reperfusion of the graft, the concentrations of serum liver enzymes and arterial lactate in the drug-treated group were significantly lower than in the control group. The postoperative increase in portal venous pressure was significantly reduced in the drug-treated group. Measurements of liver enzymes in the washed-out preservation fluid at the time of graft rinsing indicated that TAK-044 treatment of the donors significantly suppressed liver enzyme release during ischemia. CONCLUSIONS: These findings indicate TAK-044 treatment has protective effects on postoperative function of hepatic allografts procured from NHBDs. 相似文献
32.
Metastable Equilibrium Solubility Behavior of Bone Mineral 总被引:1,自引:1,他引:0
Baig AA Fox JL Wang Z Higuchi WI Miller SC Barry AM Otsuka M 《Calcified tissue international》1999,64(4):329-339
Previous studies have shown that carbonated apatites with a range of carbonate contents and crystallinities exhibit the phenomenon
of metastable equilibrium solubility (MES) distributions. The purpose of the present study was to investigate the solubility
behavior of bone mineral using the concepts of MES and MES distributions and, together with crystallinity and chemical composition
data, examine the similarity of bone mineral to carbonated apatite (CAP). Bone samples were harvested from 1-, 5-, and 8-month-old
rats. The organic components of the bone samples were removed by hydrazine deproteination. Carbonated apatite was synthesized
by the hydrolysis of dicalcium phosphate dihydrate (DCPD) in a NaHCO3-containing media at 50°C. The MES distributions of bone mineral and CAP were determined by equilibrating predetermined amounts
of CAP or bone mineral in a series of 0.1 M acetate buffers containing calculated levels of calcium and phosphate and maintained
at essentially constant pHs of 5.0, 5.3, 5.7, and 6.5. From the compositions of the equilibrating buffer solutions, ion activity
products based upon the stoichiometries of octacalcium phosphate, hydroxyapatite, and carbonated apatite were calculated in
an attempt to determine the function governing the dissolution of CAP and bone mineral. The results of this study demonstrated
that the MES distribution phenomenon appeared to hold for bone mineral and that the changes in crystallinity of bone mineral
with age correlated well with changes in the MES values. A CAP sample was prepared that was found to be an excellent synthetic
prototype closely mimicking the physicochemical behavior of bone mineral from an 8-month-old rat. Another finding of this
study was that the ion activity product function based upon the hydroxyapatite stoichiometry well described the MES results
obtained with both CAP and bone mineral. The interpretation that a surface complex with hydroxyapatite stoichiometry governs
the solubility behavior of bone mineral is, therefore, consistent with the experimental data. Other calcium phosphate stoichiometries
for the surface complex showed systematic variations in the MES profiles when the pH of the equilibrating solution was varied.
Received: 30 October 1997 / Accepted: 1 October 1998 相似文献
33.
34.
M Otsuka K Yoneoka Y Matsuda J L Fox W I Higuchi 《The Journal of pharmacy and pharmacology》1999,51(4):475-481
The effects of plasma calcium levels on oestradiol release from apatite bone cement and on the bone mineral density of ovariectomized rats have been investigated. Apatite cement was prepared from an equimolar mixture of tetracalcium phosphate, dicalcium phosphate dihydrate and 0.5% beta-oestradiol bulk powder. After subcutaneous implantation of the cement, oestradiol release in diseased rats (ovariectomized rats on a low-calcium diet) was significantly higher than in normal rats. The drug levels of recovery-model rats (ovariectomized, but on a high-calcium diet) were significantly lower than those of the diseased rats. Calcium levels in diseased rats remained low during drug release but the plasma calcium levels of the recovery-model rats increased. The areas under the plasma calcium concentration-time curves (Ca-AUCs) for the recovery-model rats were higher than those for the diseased-model rats. The plasma oestradiol concentration AUCs and the Ca-AUCs were linearly related. The body weight of the recovery-model rats increased after five days, but that of the diseased-model rats did not. The bone mass of the recovery-model rats was greater after the experiment than before. The relationship between the bone mineral density and Ca-AUC of the diseased rats suggested that bone mineral density increased with increasing Ca-AUC. The results suggest that the severity of osteoporosis in this animal model is reduced by implantation of the oestradiol-loaded apatite cement. 相似文献
35.
36.
The effect of exogenous nitric oxide on endothelial dysfunction in two-kidney, one-clip renovascular hypertensive rats 总被引:2,自引:0,他引:2
Otsuka Y Harasawa S Sugiura H Koike M Akimoto H Ishii T Abeta H Okabe T Kushiro T Kanmatsuse K 《Nihon Jinzo Gakkai shi》2000,42(8):619-624
Previous studies have shown that hypertension causes endothelial dysfunction. To study the influence of exogenous nitric oxide(NO) on endothelial dysfunction produced by hypertension, we administered a non-depressor dose of nipradilol to two-kidney, one-clip renovascular hypertensive rats(2K1C). Sprague-Dawley rats underwent either sham surgery(G-1) or clipping of the left renal artery. From day seven, 2K1C were randomized into 3 groups, placebo treatment(G-2), nipradilol treatment(G-3,) and propranolol treatment(G-4). Urinary NO2- + NO3-(NOx) excretion (UNOx V) was measured 4 weeks after clipping, and then, acetylcholine(Ach), A23187, or sodium nitroprusside(SNP)-induced relaxation were measured in the aorta. Blood pressure was increased in G-2, G-3, and G-4 compared to G-1. UNOx V was lower in G-2, G-3, and G-4 compared to G-1, but UNOx V was higher in G-3 compared to G-2 and G-4. Although Ach or A23187-induced relaxation was significantly decreased in isolated artery from G-2, G-3, and G-4 compared with those from G-1. Ach- or A23187-induced relaxation was improved in G-3. SNP-induced relaxation did not differ among the 4 groups. These results suggest that exogenous NO from nipradilol reduces the endothelial dysfunction caused by hypertension without changing the blood pressure. 相似文献
37.
BACKGROUND: The development of abnormalities in red blood cell (RBC) deformability in patients undergoing hemodialysis remains a major problem, because it is related to peripheral microcirculation, oxygen supply, and various complications in such patients. gamma-Linolenic acid (GLA; 18:3n-6), one of the polyunsaturated fatty acids and a precursor of prostaglandin E(1), is reported to have a favorable effect on the deformability of circulating blood cells in diabetic patients. METHODS: In order to clarify the efficacy of GLA on RBC deformability in 7 patients undergoing maintenance hemodialysis, we examined in a pilot study the changes in the deformability of RBC and the changes in the phospholipid fatty acid composition in both plasma and RBC membrane before and after high-dose oral supplementation with GLA derived from Mucor circinelloides for 12 weeks. RESULTS: Before supplementation, the micropore passage time of RBC suspension, which is an indicator of RBC deformability, in these patients was markedly longer than that in healthy control subjects. After administering GLA, the prolonged passage time of the patients both rapidly and steadily decreased and nearly reached control levels. Light microscopic observations of RBCs using Giemsa stain revealed a decreased number of poikilocytes after supplementation. An analysis of the fatty acid composition before treatment and 8 weeks after starting the treatment showed the dihomo-gamma-linolenic acid (DGLA; 20:3n-6) level in the plasma to have increased (p < 0.05), while the arachidonic acid (AA; 20:4n-6) concentration in the RBC membrane decreased (p < 0.05). The level of DGLA in the RBC membrane, the level of GLA, and the ratio of GLA + DGLA/AA in plasma and RBC membrane did not change significantly; however, these all tended to increase. CONCLUSION: The results of this pilot study indicate that the oral supplementation of GLA extracted from M. circinelloides improves the poor RBC deformability in hemodialysis patients, partly by inducing changes in the composition of fatty acids in plasma and RBC membrane. 相似文献
38.
39.
Kawanishi M; Kohno T; Otsuka T; Adachi J; Sone S; Noguchi M; Hirohashi S; Yokota J 《Carcinogenesis》1997,18(11):2057-2062
Allelotype and replication error (RER) phenotype analyses were performed to
clarify the pathogenetic significance of inactivation of tumor suppressor
genes and genomic instability in the genesis and progression of small cell
lung carcinoma (SCLC). We examined 37 cases of SCLC for loss of
heterozygosity (LOH) and microsatellite instability at 49 loci on all 39
nonacrocentric chromosomal arms. LOH was frequently (>70%) detected on
chromosomes 3p (29/32, 90.6%), 5q (15/21, 71.4%), 13q (25/26, 96.2%), 17p
(22/25, 88.0%), and 22q (24/33, 72.7%). Frequent LOH (>70%) on these
loci was observed even among seven cases of stage I tumors. The incidence
of LOH on all 39 nonacrocentric chromosomal arms was not significantly
different between primary tumors and metastases. These results suggest that
inactivation of multiple tumor suppressor genes accumulates relatively
early during progression of SCLC and it may be responsible for clinically
and biologically aggressive phenotype of SCLC. RER was observed in 6/37
(16.2%) of SCLC, however, RER at multiple loci was observed only in two
cases. Therefore, it was indicated that genomic instability is uncommon,
but might play a role in the genesis of a small subset of SCLC.
相似文献
40.
To investigate the functional involvement of the pineal gland in circadian expression of the rat period homolog gene (rPer2) in the suprachiasmatic nucleus (SCN) and peripheral tissues, we performed Northern blot analysis in tissues from pinealectomized rats. The ectomy did not have any significant effects on rPer2 mRNA expression patterns both in a daily light-dark condition and in a constant darkness. These results suggest that the rhythmic secretion of pineal melatonin is not essential for the circadian expression of clock genes in the SCN and other peripheral tissues of rats. 相似文献