全文获取类型
收费全文 | 5599篇 |
免费 | 262篇 |
国内免费 | 53篇 |
专业分类
耳鼻咽喉 | 56篇 |
儿科学 | 86篇 |
妇产科学 | 78篇 |
基础医学 | 617篇 |
口腔科学 | 67篇 |
临床医学 | 374篇 |
内科学 | 1611篇 |
皮肤病学 | 44篇 |
神经病学 | 413篇 |
特种医学 | 204篇 |
外科学 | 1072篇 |
综合类 | 17篇 |
一般理论 | 2篇 |
预防医学 | 122篇 |
眼科学 | 66篇 |
药学 | 513篇 |
中国医学 | 12篇 |
肿瘤学 | 560篇 |
出版年
2023年 | 28篇 |
2022年 | 56篇 |
2021年 | 81篇 |
2020年 | 50篇 |
2019年 | 78篇 |
2018年 | 84篇 |
2017年 | 60篇 |
2016年 | 105篇 |
2015年 | 100篇 |
2014年 | 149篇 |
2013年 | 145篇 |
2012年 | 230篇 |
2011年 | 271篇 |
2010年 | 149篇 |
2009年 | 143篇 |
2008年 | 269篇 |
2007年 | 263篇 |
2006年 | 252篇 |
2005年 | 248篇 |
2004年 | 229篇 |
2003年 | 244篇 |
2002年 | 237篇 |
2001年 | 219篇 |
2000年 | 223篇 |
1999年 | 211篇 |
1998年 | 58篇 |
1997年 | 38篇 |
1996年 | 36篇 |
1995年 | 33篇 |
1994年 | 41篇 |
1993年 | 21篇 |
1992年 | 143篇 |
1991年 | 147篇 |
1990年 | 155篇 |
1989年 | 176篇 |
1988年 | 126篇 |
1987年 | 134篇 |
1986年 | 110篇 |
1985年 | 112篇 |
1984年 | 68篇 |
1983年 | 47篇 |
1982年 | 22篇 |
1979年 | 38篇 |
1978年 | 27篇 |
1977年 | 19篇 |
1975年 | 18篇 |
1974年 | 24篇 |
1972年 | 28篇 |
1971年 | 23篇 |
1969年 | 20篇 |
排序方式: 共有5914条查询结果,搜索用时 203 毫秒
81.
Nishi M Takeshima H Houtani T Nakagawara K Noda T Sugimoto T 《Brain research. Molecular brain research》1999,67(1):74-81
A cDNA encoding a novel member of the small molecular weight GTP-binding protein (small G-protein) superfamily was cloned from rat spinal cord. The deduced amino acid sequence was highly homologous with those of so-far-known Rho proteins. Rho proteins were reported to alter many important cellular functions including formation of both actin stress fibers and focal adhesions. RNA blot hybridization and in situ hybridization analyses indicated that the novel small G-protein is expressed specifically in neurons in the brain and spinal cord and also in hepatic stellate cells. Based on the sequence similarity and neuron-specific expression in the brain, this protein was named RhoN. Unlike classical Rho proteins, RhoN was not susceptible to the ADP-ribosylation reaction by C3 botulinum toxin. Accordingly, RhoN seemed to be specifically involved in neuronal and hepatic functions as a C3 toxin-insensitive member of the Rho subfamily. Then, a mouse genomic DNA segment containing the RhoN gene was cloned. The locus was mapped on the mouse chromosome 11C-D. The sequence data showed that the protein-coding sequence for RhoN is divided by 4 introns, and that the defined 5 exons may encode intramolecular domains serving for different functions. 相似文献
82.
Takakura Y Tanaka Y Kumai T Sugimoto K 《The Journal of bone and joint surgery. British volume》1999,81(6):1001-1004
We studied the development of ball-and-socket deformity of the ankle by arthrography and radiography in 14 ankles of ten patients with congenital longitudinal deficiency of the fibula accompanied by various anomalies. The mean follow-up was for 18 years 10 months. In three ankles in infants less than one year old the lateral and medial sides of the ankle were already slightly round. In another seven ankles the ball-and-socket appearance developed before the age of five years. This was thought to be due to osseous coalition which limits eversion and inversion. In another four ankles in children who were over the age of one year at the initial examination, the deformity was demonstrated by arthrography and radiography at their first examination. Ball-and-socket deformity accompanied by tarsal coalition is an acquired deformity secondary to limitation of movement of the subtalar and midtarsal joints. It has completely developed by about five years of age. 相似文献
83.
Tsumura T Murata A Yamaguchi F Sugimoto K Hasegawa E Hatase O Nairn AC Tokuda M 《Vision research》1999,39(19):3165-3173
Ca2+/calmodulin-dependent protein kinase I (CaM-kinase I) in rat retina was analyzed by immunohistochemical analysis, Western blot analysis and kinase activity assay. Western blot analysis revealed two immunoreactive bands similar to those detected in the brain. Developmental studies revealed that CaM-kinase I expression increased in accordance with postnatal development. Expression of CaM-kinase I in the retinas of rats raised in the complete darkness markedly decreased. CaM-kinase I activity assay supported these findings. Synapsin I was shown to be a possible intrinsic substrate of CaM-kinase I in rat retina. These results elucidated that CaM-kinase I is expressed in the retina and may play an important role in the retinal functions and that the expression of CaM-kinase I is regulated by light stimulation. 相似文献
84.
The absorption, metabolism and excretion of NS-105 ((+)-5-oxo-D-prolinepiperidinamide monohydrate, CAS 110958-19-5), a novel cognition enhancer, were studied in rats, dogs and monkeys after intravenous or oral administration of 14C-NS-105. The protein binding of this drug was also investigated in vivo and in vitro. After the intravenous and oral administrations of 14C-NS-105, the unchanged drug accounted for most of the plasma radioactivity in all the species tested. After the intravenous injection, the plasma concentration of NS-105 decreased monoexponentially with respective elimination half-lives of 0.67, 2.1 and 1.3 h for the rats, dogs and monkeys. After the oral administration, the plasma concentration of NS-105 reached a maximum within 1 h, then decreased as in intravenous administration in all the species tested. NS-105 was almost completely absorbed from the small intestine, and first-pass metabolism was very limited. As a result, its systemic availability was high; 97% in the rats, 90% in the dogs and 79% in the monkeys. No significant sex-related differences in the plasma concentration profiles of radioactivity were observed in the rats after the oral administration of 14C-NS-105 (p > 0.05). Food affected the absorption of NS-105. The Cmax and AUC0-infinity of radioactivity concentration were proportional to the dose for 1-100 mg/kg of 14C-NS-105. There were no marked differences between the intravenous and oral routes in the compositions of urinary radioactivity for any of the species tested. In the urine of dogs, LAM-162 (oxidative metabolite with C-N cleavage of the piperidine ring), LAM-79 (metabolite with 4-hydroxylated piperidine ring), LAM-163 (metabolite with 3-hydroxylated piperidine ring) and M1 (not identified) accounted for 20%, 3%, 6% and 1% of the urinary radioactivity, respectively. In the urine of rats and monkeys, LAM-162 and LAM-79 accounted for 1-6% of the urinary radioactivity, but LAM-163 and M1 were not detected. After the intravenous and oral administrations, NS-105 was primarily eliminated by renal excretion in all the species tested, approximately 90% of the dose being excreted unchanged in the urine for rats and monkeys and 60% of it for dogs. Excretions of radioactivity in the bile and exhaled air in rats were less than 1.4% of the dose, and lymphatic absorption of radioactivity was only 0.3% of the dose. The percentage of 14C-NS-105 bound to serum proteins was less than 3.3% in all the animal species tested, including humans. 相似文献
85.
Kozutsumi D Kawashima A Sugimoto T Kotohda Y Fujimori S Takami M Kohno T Oikawa T Sugino E Choshi T Hibino S 《Biopharmaceutics & drug disposition》1999,20(6):277-284
Medroxyprogesterone acetate (MPA) is widely used in endocrine therapy for breast cancer and other diseases. Recently, it has been demonstrated that 9alpha-fluoromedroxyprogesterone acetate (FMPA) also has anti-tumour activity in chemical-induced rat mammary tumour and its activity is greater than that of MPA. In the present study, the physico-chemical properties of FMPA and MPA and their pharmacokinetics in female rats were investigated. Partition coefficients (log P) of FMPA and MPA were 3.1 and 3.8, respectively, while the solubilities of FMPA and MPA in phosphate buffer saline were 3.8 and 1.1 microg/mL, respectively. When the two agents were intravenously or orally administered into female rats, there was no significant difference between their plasma concentrations. However, unmetabolized drug excreted into urine accounted for 4.7 and 0.7% of the intravenous dose of FMPA and MPA, respectively. The free fraction of FMPA in rat plasma was approximately four times that of MPA. Assuming the well-stirred model, hepatic intrinsic clearances of FMPA and MPA were estimated to be 64 and 293 L/h per kg, respectively. In addition, the free fraction of FMPA in blood is estimated to be higher than that of MPA, which may explain the higher anti-tumour activity. 相似文献
86.
F Fujita M Fujita H Inaba T Sugimoto Y Okuyama T Taguchi 《Gan to kagaku ryoho. Cancer & chemotherapy》1991,18(13):2255-2261
HO-221, a derivative of benzoylphenylurea, is a newly developed anticancer drug which was found to show an excellent antitumor effect against transplantable murine tumors by the novel mechanism of action. This study was designed to evaluate the antitumor effect of HO-221 and to establish the optimum regimen, using seven human gastrointestinal and breast cancers xenografted in nude mice. Better antitumor effect of HO-221 by oral administration was observed when it was suspended in larger volume of the vehicle. Moreover, the effect increased by the multiple intermittent administration compared to the single treatment. Best antitumor effect was observed by oral administration of 75 mg/kg (0.1 ml/10 g mouse body weight) repeated twice weekly for a total of eight times or 300 mg/kg (0.2 ml/10 g mouse body weight) repeated once weekly for a total of four times. The antitumor effects of these two regimens were approximately equal except against H-31, the former regimen being more effective. When the tumor growth inhibition rate (IR) over 58% was rated as "effective", the above two regimens were equally effective against 4 of 7 cancers, H-111, H-154, H-143 and H-31. While HO-221 was not effective to a gastric cancer line, H-81, which was most susceptible to the variety of existing anticancer agents, but effective to another gastric cancer line, H-111, which was relatively resistant to conventional cytocidal agents. From the aspect of chemosensitivity spectrum, this drug revealed a rather different pattern compared to other antimetabolites. Although oral administration volume is limited in small animal model, enhancing its antitumor effect may be possible in clinical application by contriving the method of administration. HO-221 is, thus, considered to be a promising drug for further study. 相似文献
87.
M G Cardozo Y Iimura H Sugimoto Y Yamanishi A J Hopfinger 《Journal of medicinal chemistry》1992,35(3):584-589
QSAR analyses have been performed on the substituted indanone and benzylpiperidine ring substructures of a set of acetylcholinesterase, AChE, inhibitors of which 1-benzyl-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine hydrochloride is a potent in vitro and ex vivo inhibitor. The method of molecular decomposition-recomposition was used to define the sets of molecular substructures and corresponding in vitro inhibition databases. A QSAR involving the magnitude of the dipole moment, the highest occupied molecular orbital (HOMO) energy, and a specific pi-orbital wave function coefficient of the substituted indanone ring substructure was constructed and found to be significant. The absence of any molecular-shape or bulk term in the QSAR, coupled with some of the relatively large substituents used to construct the QSAR, suggests considerable space is available around the indanone ring during the inhibition process. A set of QSARs were constructed and evaluated for substituents on the aromatic ring of the benzylpiperidine substructure. The most significant QSAR involves a representation of molecular shape, the largest principal moment of inertia, and the HOMO of the substituted aromatic ring. It appears that upon binding the receptor "wall" is closely fit around the benzyl ring, especially near the para position. Overall, the QSAR analysis suggests inhibition potency can be better enhanced by substitution on the indanone ring, as compared to the aromatic sites of the benzylpiperidine ring. Moreover, inhibition potency can be rapidly diminished, presumably through steric interactions with the receptor surface of AChE, by substitution of moderate to large groups on the benzyl ring, particularly at the para position. 相似文献
88.
Association of decreased calcium-sensing receptor expression with proliferation of parathyroid cells in secondary hyperparathyroidism 总被引:5,自引:0,他引:5
Yano S Sugimoto T Tsukamoto T Chihara K Kobayashi A Kitazawa S Maeda S Kitazawa R 《Kidney international》2000,58(5):1980-1986
BACKGROUND: The down-regulation of both calcium-sensing receptor (CaSR) and vitamin D receptor (VDR) in parathyroid (PT) glands of secondary hyperparathyroidism (HPT) caused by chronic renal failure has been associated with PT hormone hypersecretion as well as PT hypergrowth. To clarify the predominance of decreased expression of CaSR and VDR in the high proliferative activity of PT glands, we examined the relationship between the expression of both receptors and proliferative activity in human PT glands. METHODS: Serial sections of 56 PT glands, including 52 glands from secondary HPT and 4 normal PT glands resected together with thyroid carcinoma, were examined immunohistochemically with specific antibodies against CaSR, VDR, and Ki67. The Ki67-positive cell number was counted and expressed as the Ki67 score. The CaSR and VDR expressions were semiquantitatively analyzed. RESULTS: The expressions of both CaSR and VDR were markedly decreased in PT glands of secondary HPT, while the Ki67 score was significantly higher than it was in normal controls. When hyperplastic glands were classified into two subgroups, with [N(+)] or without [N(-)] nodular formation, CaSR expression was significantly decreased in N(+), while VDR expression was not different. Multiple regression analyses revealed that the decreased expression of CaSR could contribute significantly to the high proliferative activity, even if VDR expression was taken into account. CONCLUSION: The decrease in CaSR expression is associated with the high proliferative activity of PT glands in secondary HPT, independently of the decreased VDR expression. These findings provide a new insight into the pathogenesis of PT hyperplasia, which is refractory to vitamin D therapy in patients with severe secondary HPT. 相似文献
89.
Effect of erythromycin on ischemia-reperfusion injury of liver in rats 总被引:10,自引:0,他引:10
90.
The noxious stimulus-dependent induction of c-Fos-like immunoreactivity (Fos-LI) in neurons in the subnucleus oralis and the medullary dorsal horn (MDH) was significantly suppressed by the selective destruction of unmyelinated primary neurons. The induction of Fos-LI by topical capsaicin application to the lingual mucosal stimulation was almost completely suppressed by neonatal capsaicin treatment. Fos-LI induction by the tooth pulp stimulation and by formalin injection to the lingual mucosa were only partially reduced. These results provide an evidence that the noxious signals from the intraoral structures are transmitted by both unmyelinated and myelinated nociceptors to the subnucleus oralis as well as the MDH. 相似文献