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91.
Using radioligand binding assays and postmortem normal human brain tissue, we obtained equilibrium dissociation constants (Kds) for 17 antidepressants and two of their metabolites at histamine H1, muscarinic, 1-adrenergic, 2-adrenergic, dopamine D2, serotonin 5-HT1A, and serotonin 5-HT2 receptors. Several newer antidepressants were compared with older drugs. In addition, we studied some antimuscarinic, antiparkinson, antihistamine, and neuroleptic compounds at some of these receptors. For the antidepressants, classical tricyclic antidepressants were the most potent drugs at five of the seven receptors (all but 2-adrenergic and 5-HT1A receptors). The chlorophenylpiperazine derivative antidepressants (etoperidone, nefazodone, trazodone) were the most potent antidepressants at 2-adrenergic and 5-HT1A receptors. Of ten antihistamines tested, none was more potent than doxepin at histamine H1 receptors. At muscarinic receptors antidepressants and antihistamines had a range of potencies, which were mostly weaker than those for antimuscarinics. From the in vitro data, we expect adinazolam, bupropion, fluoxetine, sertraline, tomoxetine, and venlafaxine not to block any of these five receptors in vivo. An antidepressant's potency for blocking a specific receptor is predictive of certain side effects and drug-drug interactions. These studies can provide guidelines for the clinician in the choice of antidepressant. 相似文献
92.
Disposition in mice of 7-hydroxystaurosporine,a protein kinase inhibitor with antitumor activity 总被引:1,自引:0,他引:1
Donald L. Hill Kathleen F. Tillery Lucy M. Rose Claude F. Posey 《Cancer chemotherapy and pharmacology》1994,35(1):89-92
UCN-01, a hydroxylated derivative of staurosporine, was selected for study because of its promising antitumor activity. For mice dosed intravenously, subcutaneously, or by oral gavage with this compound, the maximum tolerated doses (MTD) were 20, 10, and >100 mg/kg, respectively. UCN-01 was stable in mouse and dog plasma, but in human plasma it was converted to a metabolite in a process not inhibited by standard protease and esterase inhibitors. Following n intravenous dose of 10 mg/kg UCN-01, the half-lives for the initial (t
1/2) and terminal (t
1/2) exponential phases of elimination were 10 and 85 min, respectively; the area under the plasma concentration-time curve (AUC value) was 117 g min ml–1. In mice dosed by oral gavage with 10 mg/kg, the calculated value for the half-life of the elimination phase was 150 min. The AUC value was 15 g min ml–1, giving a value for bioavailability of 13%. After subcutaneous dosing with 10 mg/kg, the calculated values for half-lives for the distribution and elimination phases were 23 and 130 min, respectively; the AUC value was 113 g min ml–1. Since this value is equivalent to that obtained for intravenous dosing, administration of UCN-01 by the subcutaneous route may be an alternative to intravenous dosing in preclinical and clinical trials.This work was supported by contract NO1-CM-27710 (National Cancer Institute, National Institutes of Health, Department of Health and Human Services) 相似文献
93.
Purpose. The effects of 2-hydroxypropyl--cyclodextrin (HP--CD) on the aqueous solubility and stability of two lipophilic bispilocarpine prodrugs were investigated at pH 7.4.
Methods. The solubility of prodrugs was studied by phase-solubility method (0–72.5 mM HP--CD). The stability of one of the prodrugs was investigated as a function of temperature (40°C–70°C) and HP--CD concentration (0–72.5 mM). The apparent rate constants (k
1, k
2) for degradation of prodrug in 1:1 and 1:2 inclusion complexes and apparent stability constants (K
1:1, K
l:2) were calculated by the curve-fitting method.
Results. The phase-solubility diagrams were classified as Ap-type and the apparent stability constants (K
l:l, K
l:2) for 1:1- and 1:2-inclusion complexes were calculated to be 143–815 M–l and 29–825 M–1, respectively. The stability of prodrug increased as a function of HP--CD concentration over the studied temperature range. The shelf-life (t
90%, calculated by the Arrhenius equation) of the prodrug in 72.5 mM HP--CD solution increased 5.1-fold and 6.1-fold at 25°C and 4°C, respectively.
Conclusions. The solubility of the prodrugs was shown to increase markedly in phase-solubility studies. The degradation rate of prodrug in stability studies was shown to be slower in the l:2-complex than in the l:l-complex and the relative amounts of complex species were found to be dependent on CD concentration. 相似文献
94.
Susumu Furukawa Tomoyo Matsubara Toshihir Ino Keijiro Yabuta Yoshimi Umezawa Toshikazu Motohashi 《European journal of pediatrics》1994,153(9):663-667
We compared the efficacy of oral administration of pentoxifylline (PTX) and intravenous infusions of gamma globulin (IVGG) combination therapy with that of IVGG in reducing the frequency of coronary-artery lesions (CAL) in children with Kawasaki disease (KD), in a randomized trial. All patients with KD received acetylsalicylic acid (30 mg/kg per day), until the 30th day, after the onset of fever, followed by daily acetylsalicylic acid at a dose of 3-5 mg/kg per day there-after, and intravenous IVGG, 200 mg/kg per day, for 5 consecutive days. In addition, patients randomly assigned to PTX and IVGG combination therapy groups received oral PTX at a dosage of 10 mg/kg per day (low-dose) or 20 mg/kg per day (high-dose), in three divided doses until the 30th day. Patients with KD were all free from CAL prior to treatment. We assessed the presence of CAL by two-dimensional echocardiography which was also done prior to treatment and then twice a week after hospital admission. We detected CAL in 3 of 18 patients (16.7%) in the IVGG therapy group, as compared with 2 of 18 patients (11.1%) in the low-dose PTX and IVGG combination therapy group. There were no significant differences between the two groups. In the next study, we detected CAL in 3 of 21 patients (14.3%) in the IVGG therapy group, as compared with none of 22 patients (0%) in the high-dose PTX and IVGG combination therapy group (2 = 6.4, P < 0.02). No adverse side-effects were observed in 79 patients with KD. 相似文献
95.
J. Jaeken 《European journal of pediatrics》1994,153(Z1):S86-S89
We perform systematically amino acid analysis of the CSF before and after strong acid hydrolysis in children with unexplained neurological disease. By comparing the amino acid pattern before and after hydrolysis, defects can be traced in the metabolism not only of amino acids but also of purines, peptides, N-acetylated amino acids and peptides, and probably other compounds. This method has yielded important information such as the identification of two new diseases, GABA transaminase deficiency and adenylosuccinase deficiency, and the discovery of a peculiar, acid-labile double peak in the CSF of patients with the transient neonatal hyperammonaemia syndrome and with urea cycle defects. This substance was subsequently identified by others as -glutamylglutamine. As a consequence, we strongly recommend incorporating of this approach in the investigation of all children with unclear neurological disease. 相似文献
96.
《Seminars in Pediatric Surgery》2022,31(3):151181
Advancements in donor management, organ preservation and operative techniques, as well as immunosuppressive therapies, have provided children with intestinal failure and its complications a chance not only for enteral autonomy but also long-term survival through intestinal transplantation (ITx). First described in the 1960’s, experience has grown in managing these complex patients both pre- and post-transplant. The goals of this review are to provide a brief history of intestinal transplantation and intestinal rehabilitation in pediatric patients, followed by focused discussions of the indications for ITx, induction and maintenance immunosuppression therapies, common post-operative complications, and outcomes/quality of life post-transplant. 相似文献
97.
TwosignaltheoryforTcelactivationprovidedanewapproachfortumorgenetherapy[1-2].Expressionofcostimulatorymoleculegeneintransfect... 相似文献
98.
重组人骨形态发生蛋白-2/7融合基因的构建及其在大肠杆菌中的表达和初步活性测定 总被引:7,自引:0,他引:7
构建重组人骨形态发生蛋白-2/7融合体, 研究其在大肠杆菌中的表达及生物学活性。利用DNA 重组技术,将编码人骨形态发生蛋白-2 (BMP-2) 成熟肽的0.36 kb 基因片段与编码人骨形态发生蛋白-7 (BMP-7) 成熟肽的0.44kb 基因片段连接,得到重组人骨形态发生蛋白-2/7 融合基因; 经测序鉴定后,将其克隆到表达载体pBV222中,转化大肠杆菌DH5α, 温度诱导表达。表达蛋白经初步纯化后测定其对培养小鼠成骨样细胞增殖、分化及碱性磷酸酶活性的影响。克隆质粒转化的工程菌,经42℃诱导4~6 h 后,高效表达重组人骨形态发生蛋白-2/7, 在SDS-PAGE上出现一新的蛋白带, 分子量约29 ku,约占菌体总蛋白的20% ,表达蛋白以包涵体的形式存在,经初步纯化、裂解、复性后的BMP-2/7 蛋白具有促进成骨样细胞分化、增殖及增加碱性磷酸酶活性的作用。BMP-2/7 融合基因的构建和表达,可能提供一种全新的具有诱导成骨作用的蛋白 相似文献
99.
100.
Pretreatment of rats with the extract of Ginkgo biloba termed EGb761 reduced the behavioral sensitization induced by successive
-amphetamine administrations (0.5 mg/kg) as estimated by increasing values of locomotor activity. EGb761 pretreatment also prevented the reduced density of [3H]dexamethasone binding sites in the dentate gyrus and the CA1 hippocampal regions of
-amphetamine treated animals. These observations suggest that EGb761, by reducing glucocorticoid levels, could modulate the activity of the neuronal systems involved in the expression of the behavioral sensitization. 相似文献