全文获取类型
收费全文 | 3230篇 |
免费 | 130篇 |
国内免费 | 13篇 |
专业分类
耳鼻咽喉 | 11篇 |
儿科学 | 114篇 |
妇产科学 | 79篇 |
基础医学 | 553篇 |
口腔科学 | 61篇 |
临床医学 | 344篇 |
内科学 | 661篇 |
皮肤病学 | 47篇 |
神经病学 | 277篇 |
特种医学 | 51篇 |
外科学 | 254篇 |
综合类 | 13篇 |
预防医学 | 324篇 |
眼科学 | 21篇 |
药学 | 217篇 |
中国医学 | 4篇 |
肿瘤学 | 342篇 |
出版年
2024年 | 6篇 |
2023年 | 26篇 |
2022年 | 41篇 |
2021年 | 60篇 |
2020年 | 23篇 |
2019年 | 45篇 |
2018年 | 71篇 |
2017年 | 45篇 |
2016年 | 47篇 |
2015年 | 55篇 |
2014年 | 86篇 |
2013年 | 110篇 |
2012年 | 249篇 |
2011年 | 274篇 |
2010年 | 127篇 |
2009年 | 119篇 |
2008年 | 219篇 |
2007年 | 240篇 |
2006年 | 251篇 |
2005年 | 225篇 |
2004年 | 206篇 |
2003年 | 203篇 |
2002年 | 187篇 |
2001年 | 20篇 |
2000年 | 17篇 |
1999年 | 30篇 |
1998年 | 51篇 |
1997年 | 34篇 |
1996年 | 34篇 |
1995年 | 32篇 |
1994年 | 34篇 |
1993年 | 26篇 |
1992年 | 22篇 |
1991年 | 19篇 |
1990年 | 9篇 |
1989年 | 13篇 |
1988年 | 7篇 |
1987年 | 11篇 |
1986年 | 11篇 |
1985年 | 7篇 |
1984年 | 10篇 |
1983年 | 11篇 |
1982年 | 6篇 |
1981年 | 7篇 |
1977年 | 6篇 |
1976年 | 6篇 |
1975年 | 6篇 |
1973年 | 4篇 |
1972年 | 4篇 |
1971年 | 3篇 |
排序方式: 共有3373条查询结果,搜索用时 31 毫秒
11.
Anne-Marie Francois-Bellan Micheline Hery Maxime Faudon Francis Hery 《Journal of neuroendocrinology》1989,1(6):415-422
The purpose of this study was to test the capacity of oestradiol to modulate the stimulating effect of a-aminobutyric acid (GABA) on serotonin (5-HT) metabolism, previously described in the Suprachiasmatic area of the male rat. After an in vivo stimulation of GABA transmission by systemic administration of a GABA-transaminase inhibitor (amino-oxyacetic acid) or a GABAB agonist (RS-baclofen), the 5-HT metabolism was studied in the Suprachiasmatic area of ovariectomized, and ovariectomized oestradiol-treated rats. Amino-oxyacetic acid or RS-baclofen treatment increased the endogenous content of 5-HT in the Suprachiasmatic area of males and ovariectomized rats. These two treatments were without effect in ovariectomized oestradiol-treated rats. GABA transmission stimulation induced by amino-oxyacetic acid treatment failed to affect the release and synthesis of 5-HT in ovariectomized oestradiol-treated rats while it increased these two parameters of 5-HT metabolism in the Suprachiasmatic area of male and ovariectomized rats. To investigate the main target of oestradiol effect, comparative studies of the serotoninergic and GABAergic metabolism in the Suprachiasmatic area were performed in the three experimental groups. Under our experimental conditions the endogenous 5-HT metabolism was similar between ovariectomized and ovariectomized oestradiol-treated rats. Nevertheless, 5-HT metabolism was higher in the two female groups than in the male group. Neither GABA metabolism nor GABAergic response to GABA-related drug treatment differed between ovariectomized, and ovariectomized oestradiol-treated rats. However, the turnover of GABA was higher when compared to the two female groups. It is concluded that the lack of 5-HT responsiveness to GABA transmission stimulation in ovariectomized oestradiol-treated rats was not related to an effect of oestradiol on 5-HT metabolism or to an effect of the steroid on GABA turnover. Furthermore, our results suggest a sex difference in the activity of serotoninergic and GABAergic systems in the Suprachiasmatic area. 相似文献
12.
13.
Pierre Boudinot Dominique Rueff-Juy Anne-Marie Drapier Pierre-Andr Cazenave Pierre Sanchez 《European journal of immunology》1995,25(9):2499-2505
The diversity of the B cell repertoire of Cx knockout mice is limited by the expression of four λ light chain types. Among the spleen B cells, λ1 is expressed by the majority (58%) of cells, and λ3 by the minority (8%), while λ2(V2) and λ2(Vx) are expressed in intermediate quantities (18% and 16%, respectively). To assess the influence of mechanistic pressures on the λ subtype distribution, the proportions of the different λ rearrangements were determined in various B cell subpopulations divided on the basis of the λ subtype expressed, and the VλJλ junction sequences were studied at different steps of B cell differentiation (pre-B, immature and mature B cells). The data show that (1) the ratio of productive/non-productive VJ junctions is determined by the nature of the λ segments that are rearranged as can be observed in the pre-B cells, (2) V1-J1 non-productive rearrangements are often found in the λ1-negative B cells in the periphery, and (3) V1J3 junctions are often non-productive regardless of the nature of the cells analyzed. Our results, therefore, suggest that a strong probability of initiating a V1-J1 rearrangement and a weak probability of giving a productive V1J3 junction are responsible for the λ1 dominance and the λ3 under-expression, respectively. The intermediate proportion of λ2(V2) subtype is most likely due to a probability of obtaining a productive joint that is better than that for V1J3 and a probability of initiating a rearrangement that is lower than that for V1J1. However, the λ2(Vx) cell proportion cannot be determined only by these parameters. 相似文献
14.
Claire Corot Jean-Marc Idee Anne-Marie Hentsch Robin Santus Catherine Mallet Valrie Goulas Bruno Bonnemain Dominique Meyer 《Journal of magnetic resonance imaging : JMRI》1998,8(3):695-702
Transmetallation between commercially available solutions of gadolinium (Gd) chelates and the zinc (Zn)-dependent angiotensin-converting enzyme (ACE) was investigated. In vitro, the strongest inhibitions were observed for the linear Gd complexes, Gd diethylene-triamine pentaacetic acid (DTPA) bis-methylamide (BMA) (IC50 = .016 ± .006 mmol/1) and Gd-DTPA (IC50 = .350 ± .034 mmol/1). The two macrocycles Gd tetraazacyclododecane tetraacetic acid (DOTA) and Gd-HP-DO3A were similar and 400 times less active than Gd-DTPA-BMA. These effects were mainly due to the presence of free ligand for DTPA and calcium (Ca) chelate in the case of DTPA-BMA because the addition of Zn2+ in the same quantities suppresses their inhibitory effects. In vivo, these two solutions of linear Gd chelates significantly inhibited ACE activity (Gd-DTPA: 67 ± 9% versus baseline; and Gd-DTPA-BMA: 73 ± 2% versus baseline at the clinical dose of .1 mmol/kg), whereas no significant effect was observed for the two macrocyclic chelates Gd-DOTA and Gd-HP-DO3A. Formulating the Gd chelate solution with either an excess of free ligand or Ca chelate (to decrease Gd3+ release) in the case of linear Gd chelate may have deleterious biologic consequences. 相似文献
15.
Régine Ramdine Anne-Marie Galzin Salomon Z. Langer 《Naunyn-Schmiedeberg's archives of pharmacology》1989,340(4):386-395
Summary In superfused rat hypothalamic slices prelabelled with [3H]-noradrenaline, the 2-adrenoceptor agonist UK 14304 inhibited in a concentration-dependent manner the electrically-evoked release of tritium. This inhibition was antagonized by the 2-adrenoceptor blocking agent idazoxan, which by itself increased the electrically-evoked tritium overflow. Exposure to forskolin, an adenylate cyclase activator, increased the electrically-evoked release of [3H]-noradrenaline. In the presence of forskolin (1 mol/l), both the inhibitory effect of UK 14304 and the increasing effect of idazoxan on the electrically-evoked release of [3H]-noradrenaline were less pronounced than in the absence of the adenylate cyclase activator. Exposure to forskolin and to the phosphodiesterase inhibitor 3-isobutyl-l-methylxanthine shifted to the right the concentration-effect curve for UK 14304 in a similar manner as that observed in the presence of forskolin alone. Exposure to phorbol-12,13-dibutyrate (0.01–10 mol/l), a drug which activates protein kinase C, increased the electrically-evoked release of [3H]-noradrenaline. In the presence of phorbol-12,13-dibutyrate (0.1 and 1 mol/l), the concentration effect curve for UK 14304 on tritium overflow was significantly shifted to the right. The increasing effect of idazoxan on tritium overflow was significantly less pronounced in the presence of 1 mol/l phorbol-12,13-dibutyrate.In superfused rat hypothalamic slices prelabelled with [3H]-5-hydroxytryptamine, the 2-adrenoceptor agonist UK 14304 significantly inhibited the electrically-evoked release of tritium. Exposure to forskolin increased in a concentration-dependent manner [3H]-5-hydroxytryptamine overflow, but did not modify the UK 14304-mediated inhibition. Exposure to 3-isobutyl-1-methylxanthine enhanced the electrically-evoked release of [3H]-5-hydroxytryptamine. In the presence of both forskolin (1 mol/l) and 3-isobutyl-l-methylxanthine (1 mmol/l), the concentration-response curve for UK 14304 was significantly shifted to the right. Exposure to phorbol-12,13-dibutyrate (0.01–10 mol/l) enhanced in a concentration-dependent manner the electrically-evoked overflow of [3H]-5-hydroxytryptamine. In the presence of phorbol-12,13-dibutyrate (0.1 and 1 mol/l), UK 14304 was significantly less potent to inhibit tritium release than in the absence of the protein kinase C activator.It is concluded that both cyclic AMP and phosphoinositide turnover are involved in the modulation of noradrenaline and 5-hydroxytryptamine release by presynaptic 2-adrenoceptors in rat hypothalamic slices. However, these interactions do not represent definitive proof for a cause-effect relationship for the second messengers mediating the 2-adrenoceptor induced inhibition of transmitter release either as autoreceptor or as heteroreceptor.Send offprint requests to S. Z. Langer at the above address 相似文献
16.
Willis S Hutchins AM Hammet F Ciciulla J Soo WK White D van der Spek P Henderson MA Gish K Venter DJ Armes JE 《Genes, chromosomes & cancer》2003,36(4):382-392
Chromosome region 17q12-23 commonly shows an increase in DNA copy number in breast cancers, suggesting that several oncogenes are located at this site. We performed a high-resolution expression array and comparative genomic hybridization analysis of genes mapped to the entire 17q12-23 region, to identify novel candidate oncogenes. We identified 24 genes that showed significant overexpression in breast cancers with gain of 17q12-23, compared to cancers without gain. These genes included previously identified oncogenes, together with several novel candidate oncogenes. FISH analysis using specific gene probes hybridized to tissue arrays confirmed the underlying amplification of overexpressed genes. This high-resolution analysis of the 17q12-23 region indicates that several established and novel candidate oncogenes, including a Wnt-signaling pathway member, are amplified and overexpressed within individual primary breast cancer samples. We were also able to confirm the presence of two apparently separate and reciprocally amplified groups of genes within this region. Investigation of these genes and their functional interactions will facilitate our understanding of breast oncogenesis and optimal management of this disease. 相似文献
17.
Pallier C Tebourbi L Chopineau-Proust S Schoevaert D Nordmann P Testart J Courtot AM 《Human reproduction (Oxford, England)》2002,17(5):1281-1287
BACKGROUND: The effect of viral particles on the motility of human sperm and the relationship between sperm and virus are of importance particularly in assisted fertilization. METHODS: We incubated ejaculated sperm with or without seminal fluid with either herpes simplex virus type 2 (HSV2) or human cytomegalovirus (HCMV). For each experiment, 5 x 10(5) sperm were incubated with a viral load of between 10(4) and 10(6) plaque-forming units. RESULTS: We detected no apparent variations in the percentage of motile forms when sperm were incubated with either HSV2 or HCMV. Using a computer-aided semen analysis system, a slight difference was reported in the percentage of motile forms when seminal fluid-free sperm were incubated with HSV2 (57.18 versus 64.43 in the control). Although the mean amplitude of lateral head displacement and the curvilinear velocity were significantly higher in infected sperm, the difference in straight line velocity was not statistically significantly different. Few viral particles (HSV2 or HCMV) adhered to the sperm membrane in the presence of seminal fluid. However, more particles stuck when in the absence of seminal fluid, particularly with HSV2 (8% of sperm sections for HSV2; 4% for HCMV). CONCLUSIONS: The relationship between sperm and viruses depends on the type of virus present as well as the presence or absence of seminal fluid. Motility is not a good enough criterion on which to prove the presence of viral elements, either in the medium or on the sperm. 相似文献
18.
Cranial sutures and craniometric points detected on MRI 总被引:2,自引:0,他引:2
Cotton F Rozzi FR Vallee B Pachai C Hermier M Guihard-Costa AM Froment JC 《Surgical and radiologic anatomy : SRA》2005,27(1):64-70
The main goal of the study was to determine on MRI the cranial sutures, the craniometric points and craniometric measurements, and to correlate these results with classical anthropometric measurements. For this purpose, we reviewed 150 cerebral MRI examinations considered as normal (Caucasian population aged 2049 years). For each examination we individualized 11 craniometric landmarks (Glabella, Bregma, Lambda, Opisthocranion, Opisthion, Basion, Inion, Porion, Infra-orbital, Eurion) and three measurements. Measurements were also calculated independently on 498 dry crania (Microscribe 3-DX digitizer). To validate the MRI procedure, we measured four dry crania by MRI and with compass or digital caliper gauges. Cranial sutures always appeared without signal (black), whatever the MRI sequence used, and they are better visualized with a 5 mm slice thickness (compact bone overlapping). Slice dynamic analysis and multiplanar reformatting allowed the detection of all craniometric points, some of these being more difficult to detect than others (Porion, Infra-orbital). The measurements determined by these points were as follows: VertexBasion height=135.66±6.56 mm; EurionEurion width=141.17±5.19 mm; GlabellaOpisthocranion length=181.94±6.40 mm. On the midline T1-weighted sagittal image, all median craniometric landmarks can be individualized and the GlabellaOpisthocranion length, VertexBasion height and parenchyma indices can be calculated. Craniometric points and measurements between these points can be estimated with a standard cerebral MRI examination, with results that are similar to anthropometric data. 相似文献
19.
Dominique Rueff-Juy Pierre Sanchez Mathias Faure Anne-Marie Drapier Pierre-Andr Cazenave 《European journal of immunology》1995,25(10):2752-2756
Allotype- or idiotype-specific CD4+ T cells have been reported to recognize immunoglobulin (Ig) peptides presented by class II molecules. In contrast, few data are available concerning the generation of Ig peptide-specific CD8+ T cells. We have therefore investigated whether T-depleted spleen cells from Ig x light chain-expressing 129/Sv mice (129x+/+) could induce, in Cx knockout mice (129 x?/?), the generation of Ig constant x light chain region (Cx)-specific cytotoxic T lymphocytes (CTL). The determination of TCRβ chain expressed by nine CTL clones, together with the use of a library of overlapping peptides spanning the whole Cx sequence, show that the B cells from x+/+ mice are able to elicit in Cx knockout mice, the emergence of a diverse CTL repertoire that recognizes one single Cx peptide presented by the H-2Kb class I molecule. In addition, these data support the notion that B cells are able to process and present on their class I molecules, peptides generated from their own x light chains. 相似文献
20.
Marcy E. MacDonald Hamish S. Scott William L. Whaley Thomas Pohl John J. Wasmuth Hans Lehrach C. Phillip Morris Anne-Marie Frischauf John J. Hopwood James F. Gusella 《Somatic Cell and Molecular Genetics》1991,17(4):421-425
-l-Iduronidase (IDUA) has been intensively studied due to its causative role in mucopolysaccharidosis type I (Hurler, Scheie and Hurler/Scheie syndromes). The recent cloning of a human IDUA cDNA has resulted in a reevaluation of the chromosomal location of this gene. Previously assigned to chromosome 22, IDUA now has been localized to 4p16.3, the region of chromosome 4 associated with Huntington's disease (HD). The existence of a battery of cloned DNA, physical map information, and genetic polymorphism data for this region has allowed the rapid fine mapping of IDUA within the terminal cytogenetic band of 4p. IDUA was found to be coincident with D4S111, an anonymous locus displaying a highly informative multiallele DNA polymorphism. This map location, 1.1×106 bp from the telomere, makes IDUA the most distal cloned gene assigned to 4p. However, it falls within a segment of 4p16.3 that has been eliminated from the HD candidate region, excluding a role for IDUA in this disorder. 相似文献