全文获取类型
收费全文 | 31672篇 |
免费 | 1403篇 |
国内免费 | 196篇 |
专业分类
耳鼻咽喉 | 249篇 |
儿科学 | 511篇 |
妇产科学 | 241篇 |
基础医学 | 3945篇 |
口腔科学 | 739篇 |
临床医学 | 2245篇 |
内科学 | 8212篇 |
皮肤病学 | 669篇 |
神经病学 | 2447篇 |
特种医学 | 1049篇 |
外科学 | 5521篇 |
综合类 | 83篇 |
一般理论 | 4篇 |
预防医学 | 728篇 |
眼科学 | 817篇 |
药学 | 2137篇 |
中国医学 | 47篇 |
肿瘤学 | 3627篇 |
出版年
2023年 | 183篇 |
2022年 | 403篇 |
2021年 | 682篇 |
2020年 | 347篇 |
2019年 | 468篇 |
2018年 | 561篇 |
2017年 | 468篇 |
2016年 | 586篇 |
2015年 | 641篇 |
2014年 | 787篇 |
2013年 | 973篇 |
2012年 | 1631篇 |
2011年 | 1733篇 |
2010年 | 1038篇 |
2009年 | 870篇 |
2008年 | 1564篇 |
2007年 | 1696篇 |
2006年 | 1667篇 |
2005年 | 1826篇 |
2004年 | 1816篇 |
2003年 | 1644篇 |
2002年 | 1721篇 |
2001年 | 805篇 |
2000年 | 783篇 |
1999年 | 788篇 |
1998年 | 510篇 |
1997年 | 369篇 |
1996年 | 346篇 |
1995年 | 312篇 |
1994年 | 272篇 |
1993年 | 294篇 |
1992年 | 613篇 |
1991年 | 565篇 |
1990年 | 532篇 |
1989年 | 504篇 |
1988年 | 396篇 |
1987年 | 356篇 |
1986年 | 341篇 |
1985年 | 295篇 |
1984年 | 209篇 |
1983年 | 189篇 |
1982年 | 97篇 |
1981年 | 79篇 |
1979年 | 167篇 |
1978年 | 128篇 |
1977年 | 103篇 |
1974年 | 94篇 |
1973年 | 82篇 |
1972年 | 85篇 |
1971年 | 77篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
131.
Fujimoto Y Okuyama T Iijima M Tanaka T Horikawa R Yamada K Ogata T 《Molecular genetics and metabolism》2004,82(2):173-179
Although testicular development has been shown to be variably impaired in XY patients with distal 9p monosomy, ovarian and other genitourinary phenotype has poorly been studied in XX patients monosomic for the distal 9p region. Thus, we studied a 13-month-old infant with 46,XX,der(9)t(9;10)(p23;p13) (case 1) and an 11-year-old girl with 46,XX,der(9)t(9;16)(p23;q22) (case 2). Case 1 had primary hypogonadism (basal serum follicle stimulating hormone [FSH], 40.0 mIU/mL; leteinizing hormone [LH], 1.2 mIU/mL; estradiol [E2], <10 pg/mL), whereas case 2 had age-appropriate pubertal development (breast, Tanner stage 4; pubic hair, Tanner stage 3; menarche 11.7 years of age) and hormone values (FSH, 7.3 mIU/mL; LH, 6.7 mIU/mL; E2, 47 pg/mL). In addition, case 1 had hypoplastic labia majora, short distance between the vaginal orifice and the anus, and five renal cysts, and case 2 had anal atresia, short distance between the vaginal orifice and the anus, bilateral hydronephrosis of grade 3 with probable ureteropelvic junction stenosis, and renal dysfunction (serum creatinine, 1.52 mg/dL; urea nitrogen, 34.5mg/dL). Fluorescence in situ hybridization analysis for five regions and microsatellite analysis for 10 loci on 9p confirmed hemizygosity for the distal 9p region with the breakpoints between IFNA and D9S285 in case 1 and between D9S168 and D9S286 in case 2. The results, in conjunction with the previous data in XX patients with molecularly defined distal 9p monosomy, are consistent with the presence of a gene(s) involved in the development of indifferent gonad or subsequent ovarian differentiation in a approximately 11 Mb region distal to D9S168. In addition, it is possible that a gene(s) for anoperineal and renal development also maps distal to D9S168 and that for external genital development maps distal to D9S285 at the position approximately 16 Mb from the 9p telomere. 相似文献
132.
Otsuka Y Ito M Yamaguchi M Saito S Uesu K Kasai K Abiko Y Mega J 《Mechanisms of ageing and development》2002,123(6):663-674
It is well known that Down syndrome (DS) is a premature ageing syndrome. Periodontal disease in individuals with DS develops rapidly and extensively in a relatively younger age bracket compared with that in healthy controls. The mechanisms involved in the periodontal inflammatory processes in DS patients are not fully understood. In the present study, the non-inflamed gingival fibroblasts isolated from seven patients with DS (DGF) and seven healthy controls (NDGF) were stimulated with lipopolysaccharide (LPS) derived from Actinobacillus actinomycetemcomitans (A. a.). We measured the level of prostaglandin E2 (PGE2) production by DGF and NDGF by radioimmunoassay, and also measured the mRNA expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) by using the real-time PCR method. We found the higher levels of LPS-stimulated COX-2 mRNA expression and PGE2 production in DGF when compared with those in NDGF. This study may indicate that overexpression of LPS-stimulated COX-2 induced a greater ability of DGF to produce PGE2, and that these phenomena may be responsible for the severer periodontal disease in DS patients. 相似文献
133.
Hayashi M Ueda Y Yamaguchi T Sohma R Shibazaki M Ohkura T Inaba N 《American journal of reproductive immunology (New York, N.Y. : 1989)》2005,53(3):113-119
PROBLEM: Tumor necrosis factor-alpha (TNF-alpha) is present in human placental and uterine cells at the early and late stages of gestation and promotes the regulation of trophoblast growth and invasion. We evaluated whether TNF-alpha levels in the placenta and blood of pre-eclamptic women differed from those with normal pregnancies. METHOD OF STUDY: The subjects were 39 pregnant women carrying single fetuses (21 normal-pregnant and 18 pre-eclamptic patients). Their average gestational age at entry was 38-39 weeks. Peripheral blood was collected before the onset of labor and separated serum was stored at -20 degrees C. A tissue segment of the placenta was cut and frozen in liquid nitrogen immediately after delivery at -80 degrees C. The frozen placental tissue was added to phosphate-buffered saline. The tissue was fully homogenized and centrifuged. Separated supernatant was stored at -80 degrees C. TNF-alpha levels in separated serum and TNF-alpha and total protein (TP) levels in separated supernatant were measured. The presence of TNF-alpha in the placenta was evaluated by immunohistochemistry in five pre-eclamptic and five normal-pregnant patients. RESULTS: Serum TNF-alpha levels were higher in pre-eclampsia than in normal pregnancies. However, TNF-alpha/TP levels in the placenta did not differ significantly between the two groups. As for TNF-alpha immunostaining of trophoblastic cells in the placenta, it was weak in three and moderate in two of the normal pregnancies, while it was absent in two, weak in one, and moderate in two in the pre-eclampsia group. CONCLUSIONS: We demonstrated no significant increase in TNF-alpha/TP levels in the placenta in pre-eclampsia despite a significant increase in serum TNF-alpha levels. There was no strong immunostaining for TNF-alpha detected by immunohistochemistry in the pre-eclampsia group. These findings suggest that TNF-alpha in the placenta is not a key cytokine to interfere with normal trophoblast invasion into the myometrium in pre-eclampsia, and that sources other than the placenta may contribute to the elevated levels of TNF-alpha found in the circulation of pre-eclamptic patients. 相似文献
134.
Md. Iqbal Hossain Chowdhury Yoshio Koyanagi Michihiko Suzuki Susumu Kobayashi Kazuhito Yamaguchi Naoki Yamamoto 《Virus genes》1992,6(1):63-78
Syncytia or multinucleated giant-cell formation is one of the major cytopathic effects induced by human immunodeficiency virus (HIV) infection. Cell fusion results from the strong interaction of CD4 molecules on the surface of the uninfected T cells and gp120, an external envelope glycoprotein of HIV on the infected T cells. We studied the production of HIV in fusion cells between MOLT-4 and virus-infected MOLT-4/HIV cells and found that HIV production was enhanced up to three- to fivefold, which showed a good correlation with the appearance and extent of syncytia formation. Blocking the fusion by monoclonal antibody against a binding epitope of CD4 molecule to gp120 decreased the HIV production significantly. Enhancement of HIV production was observed by more than five-fold in comparison with chronically infected cells, which were fusion free 20 hr postcocultivation. Electron microscopic observation also showed the presence of abundant HIV particles inside the fused cells and on the outer surface. AZT blocked the HIV augmentation of fused cells in coculture completely. Southern blot analysis revealed that both integrated and unintegrated HIV DNA were highly accumulated in fusion cells, as compared with fusion-free MOLT-4/HIV cells. Among unintegrated DNA, circular and linear DNA were accumulated to a similar degree. Northern blot hybridization showed that rapid enhancement of all three species of HIV-specific RNA containing genomic (9.2 kb) and subgenomic (4.3 and 1.9 kb) RNAs were found 20 hr postinfection in fusion cells. These data suggest that syncytia formation is an extremely active infection process of HIV, by which multiple rounds of reinfection might take place. 相似文献
135.
Studies have suggested that psoriasis vulgaris is mediated by type 1 T cells. In this study, we examined both chemokine receptor expression and intracellular cytokine production by circulating T cells to check the type 1/type 2 balance in psoriasis. CCR4+ and CXCR3+ T cells predominantly produced interleukin-4 and interferon-, respectively. The frequency of interferon--producing cells and that of CXCR3+ cells in circulating CD4+ T cells were similar for psoriatic patients and healthy control subjects. By contrast, the frequency of CCR4+CD8+ T cells and CCR4/CXCR3 ratio in circulating CD8+ T cells were significantly higher in psoriatic patients than in healthy control subjects. Analysis of intracellular cytokine production also indicated relative increase of type 2 CD8+ T (Tc2) cells in peripheral blood from psoriatic patients. The frequency of circulating Tc2 cells directly correlated with Psoriasis Area and Severity Index. Immunohistochemical analysis showed that not only CXCR3+CD8+ T cells but also a similar number of CCR4+CD8+ T cells infiltrated the psoriatic epidermis and dermis. Our findings suggest an increase in Tc2 cell number in blood from psoriatic patients, and the association of Tc2 cells with inflammation in psoriasis. 相似文献
136.
Honma Masamitsu; Hayashi Makoto; Shimada Hiroyasu; Tanaka Noriho; Wakuri Shinobu; Awogi Takumi; Yamamoto Koichi I.; Kodani Noriko-Ushio; Nishi Yoshisuke; Nakadate Masahiro; Sofuni Toshio 《Mutagenesis》1999,14(1):5-22
In order to evaluate the utility of the mouse lymphoma assay(MLA) for detecting in vitro clastogens and spindle poisonsand to compare it with the in vitro chromosomal aberration test(CA), we conducted an international collaborative study of theMLA that included 45 Japanese laboratories and seven overseaslaboratories under the cooperation of the Ministry of Healthand Welfare of Japan and the Japanese Pharmaceutical Manufacturer'sAssociation. We examined 40 chemicals; 33 were reportedly positivein the CA but negative in the bacterial reverse mutation assay,six were negative in both assays and one was positive in both.We assayed mutations of the thymidine kinase (TK) locus (tk)of L5178Y tk+/ mouse lymphoma cells using the microwellmethod. According to our standard protocol, cells were exposedto the chemical for 3 h, cultured for 2 days and TK-deficientmutants were expressed in 96-well plates under trifluorothymidine.Each chemical was coded and tested by two or three laboratories.Among the 34 CA-positive chemicals, positive MLA results wereobtained for 20 and negative results were obtained for nine.The remaining five chemicals were inconclusive or equivocalbecause of discrepant inter-laboratory results or reproduceddiscrepant results, respectively. Among the six CA-negativechemicals, one was negative in the MLA, two were positive andthree were inconclusive. Thus, the MLA could detect only 59%(20/34) of CA-positive chemicals. We concluded that the MLAwas not as sensitive as the CA. Some MLA-negative chemicalsevoked positive responses in the CA only after long continuoustreatment. These might also be genotoxic in the MLA with longcontinuous treatment. Improvement of the MLA protocol, includingalteration of the duration of the treatment, might render theMLA as sensitive as the CA.
8 To whom correspondence should be addressed. Tel: +81 3 37009847; Fax: +81 3 3700 2348; Email: sofuni{at}nihs.go.jp 相似文献
137.
M Yamaguchi K Hirai Y Morita T Takaishi K Ohta S Suzuki K Motoyoshi O Kawanami K Ito 《International archives of allergy and immunology》1992,97(4):322-329
Human basophils were purified from normal peripheral blood, using density gradient followed by negative panning selection. We tested the effects of hemopoietic growth factors on the survival of these basophils in vitro. In the absence of exogenous factors, basophils (purity greater than 90%) decreased in number rapidly. At day 7 only 11% of the cells remained alive in cultures; less than 1% of cells survived at day 14. Interleukin (IL)-3 maintained numbers of viable cells; cell viability was 67% at day 7 and 45% at day 14. Granulocyte-macrophage (GM)-colony-stimulating factor (CSF) exhibited slight effect on the survival; 33% of cells remained at day 7. Other growth factors including granulocyte (G)-CSF, macrophage (M)-CSF, and IL-4 had no significant effect on the survival of basophils at all. Morphological and functional characterization of cells maintained by IL-3 revealed that they belonged to the basophil lineage. These observations indicate that normal basophils possess functional receptors for IL-3 and GM-CSF and that both factors modulate immediate- and delayed-type hypersensitivity reactions by prolonging the life span of basophils. 相似文献
138.
Ikegaya H Iwase H Zheng HY Nakajima M Sakurada K Takatori T Fukayama M Kitamura T Yogo Y 《Journal of virological methods》2005,126(1-2):37-43
Recently genotyping of JC virus (JCV) DNA in renal tissue was reported to be useful to identify the geographic origin of unidentified cadavers. In the above study, autopsied tissue samples without storage or stored in a frozen state were used. This study examined JCV DNA sequence modifications caused by formalin-fixation, in an attempt to elucidate whether formalin-fixed, paraffin-embedded tissue samples can also be used to determine the genotypes of JCV DNA in the kidney. In four cases, a 610 bp typing region of the JCV genome was PCR-amplified from renal tissues stored for 1 year in three different states: frozen at -80 degrees C [Amaker, B.H., Chandler, F.W., Huey, L.O., Colwell, R.M., 1997. Molecular detection of JC virus in embalmed, formalin-fixed, paraffin-embedded brain tissue. J. Forensic Sci., 1157-1159], formalin-fixed, paraffin-embedded [Ault, G.S., Stoner, G.L., 1992. Two major types of JC virus defined in progressive multifocal leukoencephalopathy brain by early and late coding region DNA sequences. J. Gen. Virol. 73, 2669-2678], and soaked in 5% formalin [Baksh, F.K., Finkelstein, S.D., Swalskey, P.A., Stoner, G.L., Ryschkewitsch, C.F., Randhawa, P.R., 2001. Molecular genotyping of BK and JC virus in human polyomavirus-associated interstitial nephritis after renal transplantation. Am. J. Kidney Dis. 38 (2), 354-365]. The amplified fragments were cloned, and the resultant clones were sequenced. In frozen samples, single sequences ('original' sequences) were detected in all cases. In formalin-fixed, paraffin-embedded samples, not only the original sequences but also those with 1-6 base substitutions were detected. From formalin-soaked samples, the original sequences and those with 1-5 and 10-13 substitutions were detected. The genotyping of JCV DNA was not hampered by the presence of 1-6 substitutions, but a shift in JCV genotypes was observed in sequences with 10-13 substitutions. Thus, it was concluded that the genotypes of JCV DNA in the kidney can be determined only with specimens stored in a frozen state or formalin-fixed for a short time. 相似文献
139.
Okubo Y Seno T Yamaguchi H Miyata Y Green CA Daniels GL 《Immunohematology / American Red Cross》1993,9(4):105-108
The first Japanese En(a-) individual (T.N.) was found by screening red cells from 250,000 Japanese blood donors with monoclonal anti-Ena. His serum contained no atypical antibodies and his partial red cell phenotype was M-N-S+s-, although a trypsin- resistant N antigen was detected. His red cells were En(a-) and Wr(b-), as determined by various human and mouse monoclonal antibodies. The absence of glycophorin A (GPA) and the presence of apparently normal glycophorin B (GPB) were demonstrated by immunoblotting with antibodies to the extracellular and cytoplasmic domain of GPA and to epitopes common to GPA and GPB. Sialic acid levels of T.N.'s intact red cells were substantially lower than those of control MN cells. Serologic tests suggested that both of T.N.'s parents were heterozygous for a recessive GPA deficiency gene. 相似文献
140.
Makoto Bannai Katsushi Tokunaga Ling Lin Atsuko Ogawa Kiyoshi Fujisawa Takeo Juji 《Human immunology》1996,46(2):107-113
We developed a system for discriminating HLA-B40, B18, B27, and B37 alleles using a two-step PCR method followed by SSCP analysis. Fragments (0.8 kb) including exon 2, intron 2, and exon 3 were amplified in the first PCR. We used two sets of primers, one specific for HLA-B60-related alleles and the other specific for HLA-B6l-related, B18, B27, and B37 alleles. No amplifications of other class I genes or pseudogenes were observed. In the second PCR, exon 2 and exon 3 were amplified separately, using diluents of the first PCR products as templates. HLA-B6l-related, B18, B27, B37, and B60-related alleles were clearly discriminated in the SSCP analysis of the second PCR products. In a population study in which B6l alleles were analyzed, B*4003 was detected in two Japanese individuals in addition to two B6l alleles previously reported to occur in Japanese, B*4002 and B*4006. The relative frequencies of B*4002, B*4006, and B*4003 in Japanese were 58, 35, and 6%, respectively. The individuals having B*4003 are the first non-South Americans in whom this allele has been detected. The SSCP banding patterns of 18 HLA-B60-positive Japanese population samples were identical to those of a B*40012 sample for both exon 2 and exon 3. We also demonstrated that the B37 allele occurring in some Japanese is B*3701. 相似文献