全文获取类型
收费全文 | 1973738篇 |
免费 | 147698篇 |
国内免费 | 3546篇 |
专业分类
耳鼻咽喉 | 29005篇 |
儿科学 | 62528篇 |
妇产科学 | 58138篇 |
基础医学 | 286796篇 |
口腔科学 | 56575篇 |
临床医学 | 170141篇 |
内科学 | 380783篇 |
皮肤病学 | 40423篇 |
神经病学 | 156121篇 |
特种医学 | 77616篇 |
外国民族医学 | 524篇 |
外科学 | 306555篇 |
综合类 | 47122篇 |
现状与发展 | 3篇 |
一般理论 | 539篇 |
预防医学 | 148745篇 |
眼科学 | 46258篇 |
药学 | 149879篇 |
1篇 | |
中国医学 | 3769篇 |
肿瘤学 | 103461篇 |
出版年
2018年 | 17888篇 |
2015年 | 17963篇 |
2014年 | 25154篇 |
2013年 | 38466篇 |
2012年 | 52472篇 |
2011年 | 55854篇 |
2010年 | 32796篇 |
2009年 | 30915篇 |
2008年 | 53690篇 |
2007年 | 58356篇 |
2006年 | 58613篇 |
2005年 | 57799篇 |
2004年 | 55955篇 |
2003年 | 54157篇 |
2002年 | 52869篇 |
2001年 | 85017篇 |
2000年 | 87254篇 |
1999年 | 74216篇 |
1998年 | 21745篇 |
1997年 | 19694篇 |
1996年 | 19750篇 |
1995年 | 18674篇 |
1994年 | 17788篇 |
1993年 | 16514篇 |
1992年 | 61361篇 |
1991年 | 60428篇 |
1990年 | 59473篇 |
1989年 | 57746篇 |
1988年 | 53887篇 |
1987年 | 52989篇 |
1986年 | 50599篇 |
1985年 | 48553篇 |
1984年 | 36887篇 |
1983年 | 31921篇 |
1982年 | 19503篇 |
1981年 | 17574篇 |
1980年 | 16355篇 |
1979年 | 35983篇 |
1978年 | 25606篇 |
1977年 | 21829篇 |
1976年 | 20470篇 |
1975年 | 22318篇 |
1974年 | 26931篇 |
1973年 | 26024篇 |
1972年 | 24712篇 |
1971年 | 22920篇 |
1970年 | 21607篇 |
1969年 | 20880篇 |
1968年 | 19353篇 |
1967年 | 17354篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
991.
992.
993.
994.
Scott S Auerbach Joshua G Dekeyser Matthew A Stoner Curtis J Omiecinski 《Drug metabolism and disposition》2007,35(3):428-439
The constitutive androstane receptor (CAR; NR1I3) regulates the expression of genes involved in xenobiotic metabolism. Alternative splicing of the human CAR gene yields an array of mRNAs that encode structurally diverse proteins. One form of CAR, termed CAR2, contains an additional four amino acids (SPTV) that are predicted to reshape the ligand-binding pocket. The current studies show a marked, ligand-independent, CAR2-mediated transactivation of reporters containing optimal DR-3, DR-4, and DR-5 response elements, and reporters derived from the natural CYP2B6 and CYP3A4 gene promoters. Overexpression of the RXRalpha ligand binding domain was critical for achieving these effects. CAR2 interaction with SRC-1 was similarly dependent on the coexpression of RXRalpha. Mutagenesis of Ser233 (SPTV) to an alanine residue yielded a receptor possessing higher constitutive activity. Alternatively, mutating Ser233 to an aspartate residue drastically reduced the transactivation capacity of CAR2. The respective abilities of these mutagenized forms of CAR2 to transactivate a DR-4 x 3 reporter element correlated with their ability to interact with RxRalpha and to recruit SRC-1 in a ligand-regulated manner. Together, these results demonstrate a robust RXRalpha-dependent recruitment of coactivators and transactivation by CAR2. In addition, CAR2 displays novel dose responses to clotrimazole and androstanol compared with the reference form of the receptor while at the same time retaining the ability to bind CITCO. This result supports a hypothesis whereby the four-amino-acid insertion in CAR2 structurally modifies its ligand binding pocket, suggesting that CAR2 is regulated by a set of ligands distinct from those governing the activity of reference CAR. 相似文献
995.
996.
Multiple intrahippocampal injections of gallamine impair performance of a representational memory task in rats. The binding of [3H]-(-)-quinuclidinyl benzilate (QNB) to rat brain sections was measured to determine if changes in receptor binding were associated with the deleterious effects of gallamine. [3H]-(-)-QNB binding to sections taken from gallamine-injected animals was compared with binding in saline-injected control animals. Autoradiographic analyses indicated an increase in [3H]-(-)-QNB binding sites within all layers of the cerebral cortex and in the superior colliculus in gallamine-treated animals as compared to saline-injected controls. Significant increases were noted in cortical layers IV and V (P less than 0.025) in gallamine-treated animals. No significant changes (P greater than 0.05) in the number of binding sites were observed in the hippocampus, neostriatum or various thalamic nuclei. The ability of unlabeled pirenzepine, gallamine and carbamylcholine to inhibit 0.2 nM [3H]-(-)-QNB binding also was measured to determine changes in the distribution of receptor subtypes. No significant changes were observed in any brain region for the binding of the selective antagonists pirenzepine and gallamine or the agonist carbamyl-choline. Although other possibilities are considered, the data suggest that an increase in the number of muscarinic receptors may contribute to the observed behavioral deficits associated with long-term gallamine treatment. 相似文献
997.
OBJECTIVES: Most obstetric clinics have a program for the identification of small-for-gestational age (SGA) fetuses because of the increased risk of fetal complications that they present. We have a structured model for the identification and follow-up of SGA pregnancies. We aimed to determine whether the recognition of SGA antepartum improves fetal outcome. METHODS: All pregnancies at Malm? University Hospital from 1990 to 1998 (n = 26 968) were reviewed. SGA fetuses identified prior to delivery (n = 681) were compared with those not identified (n = 573). Also, all pregnancies with SGA fetuses were compared with those appropriate-for-gestational age (AGA) (n = 24 585). The risk of serious fetal complications (hypoxic encephalopathy grade 2 or 3, intracranial hemorrhage, Apgar score <4 at 5 min, neonatal convulsions, umbilical pH <7.0, cerebral palsy, mental retardation, stillbirth, intrapartum or infant death) was assessed with cross-tabulation and logistic regression analysis, adjusted for gestational age and degree of SGA. RESULTS: When compared with SGA fetuses identified before delivery (54%), SGA fetuses not identified before delivery were characterized by a four-fold increased risk of adverse fetal outcome (odds ratio, 4.1; 95% CI, 2.5-6.8). Similarly, compared with AGA fetuses, SGA fetuses were associated with a four-fold increased risk of serious fetal complications. CONCLUSIONS: A structured antenatal surveillance program for fetuses identified as SGA results in a lower risk of adverse fetal outcome, compared with cases of SGA fetuses not identified antepartum. 相似文献
998.
999.
Andreas G Schatzlein Bernd H Zinselmeyer Adurrahim Elouzi Christine Dufes Ya Tsz A Chim Clive J Roberts Martyn C Davies Avril Munro Alexander I Gray Ijeoma F Uchegbu 《Journal of controlled release》2005,101(1-3):247-258
Previously, the lower generation (DAB 8-generation 2 and DAB 16-generation 3) polypropylenimine dendrimers have been shown to be effective gene delivery systems in vitro. In the current work, we sought to: (a) test the effect of the strength of the carrier, DNA electrostatic interaction on gene transfer and (b) to study the in vivo gene transfer activity of these low molecular weight (<1687 Da) non-amphiphilic plain and quaternary ammonium gene carriers. Towards this aim, methyl quaternary ammonium derivatives of DAB 4 (generation 1), DAB 8, DAB 16 and DAB 32 (generation 4) were synthesised to give Q4, Q8, Q16 and Q32, respectively. Quaternisation of DAB 8 proved to be critical in improving DNA binding, as evidenced by data from the ethidium bromide exclusion assay and dendrimer-DNA colloidal stability data. This improved colloidal stability had a major effect on vector tolerability, as Q8-DNA formulations were well tolerated on intravenous injection while a similar DAB 8-DNA dose was lethally toxic by the same route. Quaternisation also improved the in vitro cell biocompatibility of DAB 16-DNA and DAB 32-DNA dendrimer complexes by about 4-fold but not that of the lower generation DAB 4-DNA and DAB 8-DNA formulations. In contrast to previous reports with non-viral gene delivery systems, the intravenous administration of DAB 16-DNA and Q8-DNA formulations resulted in liver targeted gene expression as opposed to the lung targeted gene expression obtained with the control polymer-Exgen 500 [linear poly(ethylenimine)] and a lung avoidance hypothesis is postulated. We conclude that the polypropylenimine dendrimers are promising gene delivery systems which may be used to target the liver and avoid the lung and also that molecular modifications conferring colloidal stability on gene delivery formulations have a profound effect on their tolerability on intravenous administration. 相似文献
1000.
G K Hulse V Stalenberg D McCallum W Smit G O'neil N Morris R J Tait 《Journal of controlled release》2005,108(1):43-55
In order to assess the histological tissue changes over time around the site of implant, tissue biopsies were taken at 1 to 38 months post-implant from 54 (34 male) consenting human subjects who had received the Australian subcutaneous naltrexone-poly(DL-lactide) implant for heroin dependence. The implant consists of multiple tablets containing compressed naltrexone-poly[trans-3,6-dimethyl-1,4-dioxane-2,5-dione] (DL-lactide) loaded microspheres. Assessment of tissue samples by pathologists showed an early phase (up to 12 months post-implant) of inflammation, foreign body reaction, and fibrosis. This subsided gradually over the next 12 months until tissue returned to normal by 25+ months. Sufficient evidence was not available to conclude that the poly(DL-lactide) implant matrix was totally biodegradable within the study period. While implant material was not identified in most of the latter biopsies, its presence was noted in one biopsy at 26 months post-implant. Nevertheless the study results did demonstrate the implant's biocompatibility by the lack of inflammation, foreign body reaction, and fibrosis detected by 25+ months. It seems highly probable that surgical technique rather than the implant itself was associated with the additional finding of fat necrosis. Moderate fat necrosis was observed as a common feature of biopsies carried out during the first 6 months following implant. It subsided to mild levels over the next 18 months, and was notably absent by 25+ months. The results of the study indicated that the Australian naltrexone-poly(DL-lactide) implant is well tolerated and may have a role for use in the management of medical conditions such as heroin dependence. 相似文献