全文获取类型
收费全文 | 1295篇 |
免费 | 59篇 |
国内免费 | 7篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 20篇 |
妇产科学 | 11篇 |
基础医学 | 161篇 |
口腔科学 | 25篇 |
临床医学 | 58篇 |
内科学 | 237篇 |
皮肤病学 | 3篇 |
神经病学 | 144篇 |
特种医学 | 22篇 |
外科学 | 334篇 |
综合类 | 3篇 |
预防医学 | 32篇 |
眼科学 | 43篇 |
药学 | 66篇 |
肿瘤学 | 198篇 |
出版年
2023年 | 8篇 |
2022年 | 19篇 |
2021年 | 36篇 |
2020年 | 22篇 |
2019年 | 26篇 |
2018年 | 24篇 |
2017年 | 25篇 |
2016年 | 21篇 |
2015年 | 28篇 |
2014年 | 32篇 |
2013年 | 42篇 |
2012年 | 56篇 |
2011年 | 66篇 |
2010年 | 60篇 |
2009年 | 37篇 |
2008年 | 75篇 |
2007年 | 87篇 |
2006年 | 84篇 |
2005年 | 88篇 |
2004年 | 82篇 |
2003年 | 71篇 |
2002年 | 65篇 |
2001年 | 14篇 |
2000年 | 23篇 |
1999年 | 19篇 |
1998年 | 19篇 |
1997年 | 15篇 |
1996年 | 10篇 |
1995年 | 11篇 |
1994年 | 11篇 |
1993年 | 10篇 |
1992年 | 15篇 |
1991年 | 11篇 |
1990年 | 11篇 |
1989年 | 10篇 |
1988年 | 7篇 |
1987年 | 7篇 |
1984年 | 11篇 |
1983年 | 8篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1979年 | 5篇 |
1977年 | 6篇 |
1973年 | 5篇 |
1972年 | 8篇 |
1971年 | 10篇 |
1970年 | 9篇 |
1969年 | 8篇 |
1968年 | 5篇 |
1967年 | 5篇 |
排序方式: 共有1361条查询结果,搜索用时 0 毫秒
1.
Shiro Akinaga Tadashi Ashizawa Katsushige Gomi Hiroe Ohno Makoto Morimoto Chikara Murakata Masami Okabe 《Cancer chemotherapy and pharmacology》1992,29(4):266-272
Summary Novel derivatives of K-252a, (8R*,9S*,11S*)-(–)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8, 11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo [a,g]-cycloocta[cde]trinden-1-one, an inhibitor of protein kinases and calmodulin-dependent phosphodiesterase, were synthesized and evaluated for their antitumor activity in vitro and in vivo. Of ten derivatives tested, four were active against the P388 murine leukemia i. p.-i. p. system, although K-252a was inactive. Among these derivatives, KT6124 was selected for further biological evaluation studies because its efficacy was the highest. KT6124 was also active against sarcoma 180 and B16 melanoma. It exerted a relatively broad spectrum of antiproliferative activity against 20 human tumor cell lines in vitro. To determine the mechanism(s) of action underlying the antitumor activity of KT6124, we tested the drug for inhibition of protein kinases, including Ca2+-and phospholipid-dependent protein kinase (PKC), in intact A431 human epidermoid carcinoma cells in comparison with the PKC-inhibitory activity of K-252a. KT6124 did not antagonize the action of phorbol 12-myristate 13-acetate (PMA) in A431 cells, whereas K-252a did, suggesting that KT6124 may not act on protein kinases in the cells. The interaction of KT6124 with DNA in living cells was examined by the alkaline elution method. KT6124 apparantly exhibited DNA scission both dose-and time-dependently in the target cells. The DNA breakage was dependent on proteinase K treatment, suggesting its possible interaction with DNA-related enzyme(s). These results indicate that KT6124 exerts antitumor activity by acting on DNA or on DNA-related enzyme(s) in tumor cells rather than via the inhibition of protein kinases. 相似文献
2.
Hiroko Ida-Yonemochi Wael Swelam Chikara Saito Takashi Saku 《Journal of oral pathology & medicine》2005,34(1):59-61
A case of angiolipoma occurring in the buccal mucosa of a 69-year-old male is described. The patient had noticed a painless mass in his buccal mucosa for 2 years. The surgically removed tumor, measuring 9 mm in diameter, was mainly located in the submucosal layer with focal expansion into the muscle layer. Histologically, the tumor was well-demarcated and composed of proliferations of mature fat cells and fibrous connective tissue containing many small blood vessels, which were evenly distributed. There was diffuse infiltration of a large number of mast cells, which were immunopositive for vascular endothelial growth factor (VEGF) especially around blood vessels, suggesting that VEGF produced by mast cells in angiolipomas plays an important role in the vascular proliferation in this particular tumor. 相似文献
3.
Increased 5-HT-2 receptor function as measured by serotonin-stimulated phosphoinositide hydrolysis in platelets of depressed patients. 总被引:2,自引:0,他引:2
M Mikuni I Kusumi A Kagaya Y Kuroda H Mori K Takahashi 《Progress in neuro-psychopharmacology & biological psychiatry》1991,15(1):49-61
1. The present study was undertaken to examine whether or not 5-HT-induced inositol monophosphate (IP-1) accumulation in human platelets is mediated by 5-HT-2 receptors and to assess 5-HT-2 receptor function as measured by 5-HT-stimulated IP-1 accumulation in platelets from normal controls and depressed patients before drug treatment. 2. In platelets prelabeled with 3H-myo-inositol, in Ca ion free HEPES buffer containing 10 mM LiCl, 5-HT caused a dose-dependent accumulation of IP-1 during 15 min incubation. A maximal increase in IP-1 formation was observed at 30 microM of 5-HT and its EC50 value was 4 microM. 3. Ketanserin, a selective 5-HT-2 antagonist, was a potent inhibitor of 5-HT-stimulated IP-1 accumulation with a Ki value of 12 nM, but (-)propranolol (10 microM), a 5-HT-1 antagonist, failed to block the 5-HT response. 4. The potencies of various compounds tested to inhibit 5-HT-stimulated IP-1 accumulation in human platelets correlated positively with the affinities to 5-HT-2 receptor as defined by radioligand binding in rat cerebral cortex. 5. In a group of unmedicated patients with major depressive disorder matched for age with normal control group, we found a significant increase in 5-HT (100 microM)-induced accumulation of IP-1 (150 +/- 7% of basal for depressed patients, 132 +/- 3% for controls). 相似文献
4.
Yoshitomo Kashiwagi Chikara Kikuchi Jun-ichi Anzai 《Journal of electroanalytical chemistry (Lausanne, Switzerland)》2002,518(1):51-55
Electrocatalytic dehalogenation of organohalides was studied using a nickel(II) tetraazamacrocyclic complex-modified graphite felt electrode. The nickel(II) tetraazamacrocyclic complex-modified graphite felt electrode was prepared by attaching nickel(II) (6-(2′-hydroxyethyl)-1,4,8,11-tetraazacyclotetradecane)perchlorate chemically to the carboxyl groups of a thin poly(acrylic acid) layer coated on the graphite felt. The modified electrode gave a reversible electron transfer for the nickel(II)/nickel(I) redox couple in cyclic voltammetry at ?0.95 V versus Ag/AgCl. A preparative electrocatalytic dehalogenation of organohalides was successfully achieved on the modified electrode with an adequate current efficiency (55.6–94.8%), conversion (34.2–100%) and turnover number of the Ni catalyst (667–3333). 相似文献
5.
The complete nucleotide sequence of rice tungro spherical virus (RTSV) strain Vt6, originally from Mindanao, the Philippines, with higher virulence to resistant rice cultivars, was determined and compared with the published sequence for the Philippine-type strain A (RTSV-A-Shen). It was reported that RTSV-A was not able to infect a rice resistant cultivar TKM 6 (10). RTSV-Vt6 and RTSV-A-Shen share 90% and 95% homology at nucleotide and amino-acid levels, respectively. The N-terminal leader sequence of RTSV-Vt6 contained a 39-amino acids-region (positions 65 to 103) which was totally different from that of RTSV-A-Shen; the difference resulted from frame shifting by nucleotide insertions and deletions. To confirm the amino-acid sequence differences of the leader polypeptide, the same region was cloned and sequenced using a newly obtained variant of RTSV-type 6, which had been collected in the field of IRRI, and seven field isolates from Mindanao, the Philippines. Since all the sequences of the target region are identical to that of the Vt6 leader polypeptide, the sequence difference in the leader region seems not to correlate with the virulence of Vt6. 相似文献
6.
Seminoma in a postmenopausal woman with a Y;15 translocation in peripheral blood lymphocytes and a t(Y;15)/45,X Turner mosaic pattern in skin fibroblasts.
下载免费PDF全文
![点击此处可从《Journal of medical genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
N Hoshi M Fujita M Mikuni T Fujino K Okuyama Y Handa H Yamada T Sagawa H Hareyama Y Nakahori K Fujieda J A Kant K Nagashima S Fujimoto 《Journal of medical genetics》1998,35(10):852-856
We report an unusual case of a 55 year old Japanese woman with a seminoma but relatively normal menses. The patient was a phenotypic female with late onset menarche (18 years of age), who was amenorrhoeic for the first year, followed by menses of one to three days' slight flow with dysmenorrhoea, but an otherwise normal menstrual history. A typical seminoma was removed from the left adnexal region and an immature testis was identified separately as an associated right adnexal mass. Repeated karyotypic studies on peripheral blood lymphocyte cultures showed only 46,X,-Y,t(Y;15)(q12;p13). Cytogenetic examination of the patient's younger brother, who had fathered three healthy children, showed an identical karyotype. Mosaicism of 46,X,-Y,t(Y;15)(q12;p13)/45,X cell lines was found in skin samples from the patient's elbow and genital regions, although there were no clinical stigmata of Turner syndrome. An androgen receptor binding assay of cultured genital skin fibroblasts was negative. Molecular analysis using Southern blot hybridisation, PCR, and direct DNA sequencing showed that neither the patient nor her brother had a detectable deletion or other abnormalities of Y chromosome sequences, including the SRY (sex determining region of the Y chromosome) gene sequence. These findings suggest that Turner mosaicism of the 45,X cell line may have contributed to this atypical presentation in an XY female, although we cannot exclude abnormalities of other genes related to sex differentiation. 相似文献
7.
Molecular cloning and complete nucleotide sequence of the genome of Japanese encephalitis virus Beijing-1 strain 总被引:5,自引:0,他引:5
Hiroshi Hashimoto Akio Nomoto Koji Watanabe Takayuki Mori Toshiyuki Takezawa Chikara Aizawa Tsutomu Takegami Keiichi Hiramatsu 《Virus genes》1988,1(3):305-317
The genomic RNA of the Japanese encephalitis virus (JEV) Beijing-1 strain was reversely transcribed and the synthesized cDNA was molecularly cloned. Six continuous cDNA clones that cover the entire virus genome were established and sequenced to determine the complete nucleotide sequence of the JEV RNA. The precise genomic size was estimated as 10,965 bases long. With flanking 95 bases at the 5 and 583 bases at the 3 non-coding regions, one long open reading frame (ORF) was revealed encoding a virus polyprotein with 3,429 amino acid residues. Because of sequence homologies observed between JEV and other flaviviruses, the genome organization of JEV appears to be identical with other flaviviruses. Genetic variation detected among flavivirus genomes is consistent with the established serological relatedness between JEV and other members of flaviviruses. The secondary structure of the JEV genome is deduced and discussed concerning its involvement in genome replication. 相似文献
8.
Saito A Suzuki Y Ogata S Ohtsuki C Tanihara M 《Journal of biomedical materials research. Part A》2004,70(1):115-121
Bone morphogenetic protein-2 (BMP-2) promotes the formation and regeneration of bone and cartilage, and therefore constitutes the most promising candidate for a bone repair material. However, it also has a wide range of functions, such as in organogenesis and apoptosis. Therefore, we investigated a novel synthetic peptide corresponding to residues 73-92 of BMP-2. This peptide bound to a BMP-2-specific receptor and elevated both alkaline phosphatase activity and osteocalcin mRNA in the murine cell line, C3H10T1/2. The 73-92 peptide also induced ectopic calcification when conjugated to a covalently crosslinked alginate gel. Here we report that the 73-92 peptide-conjugated alginate gel showed prolonged ectopic calcification for up to 7 weeks in rat calf muscle. In contrast, rhBMP-2-impregnated collagen gel showed maximum ectopic calcification at 3 weeks, and the calcified products that had formed disappeared after 5 weeks. Histological examination showed that the 73-92 peptide-conjugated alginate gel induced many osteoblast-like cells and few osteoclasts. In contrast, rhBMP-2-impregnated collagen gel induced many osteoclasts. These results suggest that the 73-92 peptide on alginate gel remains active at the implanted site, continuously induces differentiation of osteoblast precursor cells into osteoblasts, and activates osteoblasts to promote ectopic calcification. 相似文献
9.
Akagi M Inui K Nakajima S Shima M Nishigaki T Muramatsu T Kokubu C Tsukamoto H Sakai N Okada S 《Journal of human genetics》2000,45(1):60-62
Fanconi-Bickel syndrome (FBS), or glycogen storage disease type XI, is a rare autosomal recessive disorder characterized
by hepatorenal glycogen accumulation, Fanconi nephropathy, and impaired utilization of glucose and galactose. Recently, this
disease was elucidated to link mutations in the glucose transporter 2 (GLUT2) gene. Only three mutations in three FBS families have been reported. Therefore, it is important to elucidate mutations in
the GLUT2 gene in FBS by answering the question of whether the syndrome is a single gene disease. In this report, we describe two patients
in two unrelated families clinically diagnosed with FBS. No mutation in the entire protein coding region of the GLUT2 gene was detected in patient 1, which suggested that no mutation existed in the GLUT 2 gene, or that some mutations had affected the expression of the GLUT 2 gene. In patient 2, a novel homozygous nonsense mutation (W420X, Trp at codon 420 to stop codon) was detected. These results
support the correlation between GLTU2 gene mutation and FBS syndrome. However, many patients must be analyzed to determine whether other genes are involved in
FBS.
Received: July 16, 1999 / Accepted: September 3, 1999 相似文献
10.
Evidence for the involvement of blood flow-related mechanisms in the ovulatory process of the rat 总被引:7,自引:0,他引:7
Zackrisson U Mikuni M Peterson MC Nilsson B Janson PO Brännström M 《Human reproduction (Oxford, England)》2000,15(2):264-272
To elucidate whether any relationship exists between ovarian blood flow and ovulation rate, the effects on these parameters were examined in equine chorionic gonadotrophin/human chorionic gonadotrophin (eCG/HCG) (15I U/15I U) primed rats after bilateral ligation and severance of either the ovarian branch of the uterine artery and vein (UL), the ovarian artery and vein (OL) or both sites (UL+OL) in comparison to sham operations. Laser Doppler flowmetry demonstrated the presence of microcirculatory vasomotion and a reduction of blood flow after UL, OL and UL+OL performed during the intervals 0-3 h (78, 66 and 19% of pretreatment values respectively) and 6-9 h (68, 57 and 20%) after HCG. Experiments utilizing radioactive microspheres also indicated decreased ovarian blood flow by UL and OL. Ovulation rate was assessed 20 h after HCG in animals where ligations had been performed at 0, 3, 6 and 9 h after HCG. No ovulations were seen after UL+OL and significantly decreased ovulation rates ( approximately 50% of sham operated animals) were seen after UL at 0 and 3 h and after OL at 0, 6 and 9 h. Progesterone concentrations in blood 20 h after HCG were reduced by OL but not UL and ovarian weights were unaffected by ligation. It is concluded that acute blood flow reduction during the ovulatory interval reduces ovulation rate in the rat. 相似文献