全文获取类型
收费全文 | 8587篇 |
免费 | 442篇 |
国内免费 | 73篇 |
专业分类
耳鼻咽喉 | 109篇 |
儿科学 | 206篇 |
妇产科学 | 39篇 |
基础医学 | 918篇 |
口腔科学 | 208篇 |
临床医学 | 567篇 |
内科学 | 2103篇 |
皮肤病学 | 182篇 |
神经病学 | 584篇 |
特种医学 | 318篇 |
外科学 | 1402篇 |
综合类 | 36篇 |
预防医学 | 202篇 |
眼科学 | 342篇 |
药学 | 980篇 |
中国医学 | 10篇 |
肿瘤学 | 896篇 |
出版年
2023年 | 52篇 |
2022年 | 129篇 |
2021年 | 240篇 |
2020年 | 153篇 |
2019年 | 171篇 |
2018年 | 237篇 |
2017年 | 170篇 |
2016年 | 220篇 |
2015年 | 237篇 |
2014年 | 271篇 |
2013年 | 336篇 |
2012年 | 559篇 |
2011年 | 579篇 |
2010年 | 367篇 |
2009年 | 303篇 |
2008年 | 550篇 |
2007年 | 569篇 |
2006年 | 550篇 |
2005年 | 518篇 |
2004年 | 474篇 |
2003年 | 434篇 |
2002年 | 423篇 |
2001年 | 123篇 |
2000年 | 134篇 |
1999年 | 152篇 |
1998年 | 88篇 |
1997年 | 76篇 |
1996年 | 75篇 |
1995年 | 61篇 |
1994年 | 43篇 |
1993年 | 41篇 |
1992年 | 88篇 |
1991年 | 70篇 |
1990年 | 67篇 |
1989年 | 73篇 |
1988年 | 64篇 |
1987年 | 48篇 |
1986年 | 36篇 |
1985年 | 44篇 |
1984年 | 45篇 |
1983年 | 25篇 |
1982年 | 25篇 |
1981年 | 23篇 |
1980年 | 17篇 |
1979年 | 29篇 |
1978年 | 14篇 |
1977年 | 10篇 |
1976年 | 9篇 |
1974年 | 12篇 |
1969年 | 9篇 |
排序方式: 共有9102条查询结果,搜索用时 31 毫秒
61.
Yoshihiko Takahashi Yuichi Takiguchi Takayuki Kuriyama Tadaaki Miyamoto 《Clinical & experimental metastasis》1998,16(2):149-157
A clone of NIH3T3 transformant (H3) can yield subcutaneous tumors and experimental pulmonary metastasis in nude mice. Compared
to H3 in culture, the cells after in vivo tumor growth (H3-N) acquired enhanced tumorigenicity and metastatic ability. Also, indirect immunofluorescence revealed that
cellular fibronectin (c-FN) of H3-N was decreased remarkably. We have studied the interactions between H3 and extracellular
matrices to elucidate these phenomena. In the present study, we observed the effect of NIH3T3, H3, and H3-N cultured in type
I collagen gel. Morphologically in the collagen gel, NIH3T3 assumed an extensive elongated fiber-like shape, H3 assumed a
moderately elongated shape, and H3-N assumed a round or spindle shape with short pseudopodia. Compared to conventional cultures
on dishes, cell proliferation of all three types was suppressed in collagen gel, but the degree of the suppression was least
in H3-N. As a result, H3-N grew fastest in collagen gel. The variants which acquired growth advantage in the subcutaneum of
mice also kept it in collagen gel. H3 cells were cultured in type I collagen gel for 4 weeks, a period comparable to that
of tumor formation in nude mice. The cells after this long-term culture (H3-C) acquired enhanced tumorigenicity and metastatic
ability nearly equal to that of H3-N. FACS analysis revealed that the c-FN of H3-C had decreased to a value comparable to
that of H3-N. This means that type I collagen gel as well as subcutaneous tissues could select variants of H3 with less c-FN
through proliferation. Moreover, it is suspected that lattices of type I collagen regulate cell proliferation of fibroblast
via c-FN.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
62.
Adjuvant Activity of 6-Amino-6-Deoxy-Muramyldipeptides and Their Acylamino Derivatives on the Induction of Delayed Hypersensitivity to Azobenzenearsonate-N-Acetyl-l-Tyrosine in Guinea Pigs 下载免费PDF全文
Ichiro Azuma Hiroyuki Okumura Ikuo Saiki Yoshiro Tanio Makoto Kiso Akira Hasegawa Yuichi Yamamura 《Infection and immunity》1981,32(3):1305-1308
The 6-amino-6-deoxy-N-acetylmuramyldipeptides and their 6-acylamino derivatives were shown to be active as adjuvants on the induction of delayed-type hypersensitivity to azobenzenearsonate-N-acetyl-l-tyrosine in guinea pigs. However, 6-acylamino-6-deoxy-N-(acyl)muramyldipeptides were inactive as adjuvants. 相似文献
63.
Takusa Y Fukao T Kimura M Uchiyama A Abo W Tsuboi Y Hirose S Fujioka H Kondo N Yamaguchi S 《Molecular genetics and metabolism》2002,75(3):227-234
Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is clinically classified into severe, intermediate, and myopathic forms. We identified mutations in three unrelated Japanese patients with VLCAD deficiency: two with the myopathic form and one with the intermediate form, all compound heterozygotes of K264E/M437V, A416T/1798delA, and P89S/IVS16-3delAA, respectively. We characterized four missense mutations, K264E, M437V, A416T, and P89S, by transisent expression analysis, using SV40-transformed fibroblasts derived from a VLCAD-null patient, as recipient cells. In transient expression of the wild-type VLCAD cDNA, VLCAD activity at 30 degrees C was higher than at 37 degrees C. Moreover, this temperature-sensitive character is more evident in all the mutant proteins tested than in wild type. Based on characterization of the five missense mutations identified in four Japanese patients, including data on one patient with the myopathic form previously reported, patients with the nonsevere forms (intermediate or myopathic forms) have missense mutations with residual activities in at least one allele. Expression analysis at 30 degrees C may be more useful for evaluating these missense mutations, compared with that at 37 degrees C. 相似文献
64.
Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure 总被引:15,自引:0,他引:15
Ikezuki Y Tsutsumi O Takai Y Kamei Y Taketani Y 《Human reproduction (Oxford, England)》2002,17(11):2839-2841
BACKGROUND: There is broad human exposure to bisphenol A (BPA), an estrogenic endocrine-disrupting chemical widely used for the production of plastic products. BPA is reported to affect preimplantation embryos or fetuses and alter their postnatal development at doses typically found in the environment. We measured contamination of BPA in various kinds of human biological fluids by a novel enzyme-linked immunosorbent assay. METHODS: Blood samples were obtained from healthy premenopausal women, women with early and full-term pregnancy, and umbilical cord at full-term delivery. Ovarian follicular fluids obtained during IVF procedures and amniotic fluids obtained at mid-term and full-term pregnancy were also subject to BPA measurements. RESULTS: BPA was present in serum and follicular fluid at approximately 1-2 ng/ml, as well as in fetal serum and full-term amniotic fluid, confirming passage through the placenta. Surprisingly, an approximately 5-fold higher concentration, 8.3 +/- 8.7 ng/ml, was revealed in amniotic fluid at 15-18 weeks gestation, compared with other fluids. CONCLUSION: These results suggest accumulation of BPA in early fetuses and significant exposure during the prenatal period, which must be considered in evaluating the potential for human exposure to endocrine-disrupting chemicals. 相似文献
65.
Yuji Narita Hideaki Kagami Hiroshi Matsunuma Yosuke Murase Minoru Ueda Yuichi Ueda 《Journal of artificial organs》2008,11(2):91-99
Previous attempts to create small-caliber vascular prostheses have been limited. The aim of this study was to generate tissue-engineered small-diameter vascular grafts using decellularized ureters (DUs). Canine ureters were decellularized using one of four different chemical agents [Triton-X 100 (Tx), deoxycholate (DCA), trypsin, or sodium dodecyl sulfate (SDS)] and the histology, residual DNA contents, and immunogenicity of the resulting DUs were compared. The mechanical properties of the DUs were evaluated in terms of water permeability, burst strength, tensile strength, and compliance. Cultured canine endothelial cells (ECs) and myofibroblasts were seeded onto DUs and evaluated histologically. Canine carotid arteries were replaced with the EC-seeded DUs (n = 4). As controls, nonseeded DUs (n = 5) and PTFE prostheses (n = 4) were also used to replace carotid arteries. The degree of decellularization and the maintenance of the matrix were best in the Tx-treated DUs. Tx-treated and DCA-treated DUs had lower remnant DNA contents and immunogenicity than the others. The burst strength of the DUs was more than 500 mmHg and the maximum tensile strength of the DUs was not different to that of native ureters. DU compliance was similar to that of native carotid artery. The cell seeding test resulted in monolayered ECs and multilayered alpha-smooth muscle actin-positive cells on the DUs. The animal implantation model showed that the EC-seeded DUs were patent for at least 6 months after the operation, whereas the nonseeded DUs and PTFE grafts become occluded within a week. These results suggest that tissue-engineered DUs may be a potential alternative conduit for bypass surgery. 相似文献
66.
Yuichi Takeoka Shao-Yuan Chen Richard L. Boyd Koichi Tsuneyama Nobuhisa Taguchi Shinji Morita Hisashi Yago Seishi Suehiro Aftab A. Ansari Leonard D. Shultz M. Eric Gershwin 《Clinical & developmental immunology》1997,5(2):79-89
It is widely accepted that the thymic microenvironment regulates normal thymopoiesis
through a highly coordinated and complex series of cellular and cytokine interactions. A direct
corollary of this is that abnormalities within the microenvironment could be of etiologic
significance in T-cell-based diseases. Our laboratory has developed a large panel of
monoclonal antibodies (mAbs) that react specifically with epithelial or nonepithelial
markers in the thymus. We have taken advantage of these reagents to characterize the
thymic microenvironment of several genetic strains of mice, including BALB/cJ,
C57BL/6J, NZB/BlnJ, SM/J, NOD/Ltz, NOD/Ltz-scid/sz, C57BL/6J-Hcph
me/Hcph me, and
ALY/NscJcl-aly/aly mice, and littermate control animals. We report herein that control
mice, including strains of several backgrounds, have a very consistent phenotypic profile
with this panel of monoclonal antibodies, including reactivity with thymic epithelial cells
in the cortex, the medulla and the corticomedullary junction, and the extracellular matrix.
In contrast, the disease-prone strains studied have unique, abnormal staining of thymic cortex
and medulla at both the structural and cellular levels. These phenotypic data suggest
that abnormalities in interactions between developing thymocytes and stromal cells characterize
disease-prone mice. 相似文献
67.
68.
Tokuhiro Ishihara Yoshimi Yamashita Yoshiko Okuzono Tadaaki Yokota Mutsuo Takahashi Toshiaki Kamei Fumiya Uchino Noboru Matsumoto Shiro Miwa Hisaichi Fuji Takeshi Kozaki 《Ultrastructural pathology》1985,8(1):13-23
By light and electron microscopy, we observed foamy cells in the spleens from a patient with hemolytic anemia due to red cell adenosine deaminase (ADA) overproduction, a patient with rheumatoid arthritis (RA) treated with gold, and patients with idiopathic thrombocytopenic purpura (ITP)
The foamy cells associated with red cell ADA overproduction were essentially similar to Gaucher-like cells described in patients with thalassemia, and it was suggested that the accelerated destruction of red cells was one of the factors responsible for the development of foamy cells. Foamy cells in ITP and RA were closely associated with an increased destruction of platelets in the spleen. Morphologic transitions between phagocytosed platelets and myelinlike materials were traced in these disorders. In RA, however, foamy cells were heterogeneous from an ultrastructural standpoint, with different cytoplasmic inclusions. In addition to myelinlike materials, dense bodies, vacuoles with flocculent materials, and gold were noted in most of foamy cells. As gold compounds are known to inhibit lysosomal enzymes, we surmise that an acquired disturbance in lysosomal digestion is partially responsible for the accumulation of intermediate metabolites.
In the pathogenesis of foamy cells associated with blood cell dyscrasia, the accelerated destruction of blood cells and/or acquired disorders in catabolic pathways within the macrophages are suggested to be the underlying mechanism of an intralysosomal accumulation of incompletely degraded cellular debris. 相似文献
The foamy cells associated with red cell ADA overproduction were essentially similar to Gaucher-like cells described in patients with thalassemia, and it was suggested that the accelerated destruction of red cells was one of the factors responsible for the development of foamy cells. Foamy cells in ITP and RA were closely associated with an increased destruction of platelets in the spleen. Morphologic transitions between phagocytosed platelets and myelinlike materials were traced in these disorders. In RA, however, foamy cells were heterogeneous from an ultrastructural standpoint, with different cytoplasmic inclusions. In addition to myelinlike materials, dense bodies, vacuoles with flocculent materials, and gold were noted in most of foamy cells. As gold compounds are known to inhibit lysosomal enzymes, we surmise that an acquired disturbance in lysosomal digestion is partially responsible for the accumulation of intermediate metabolites.
In the pathogenesis of foamy cells associated with blood cell dyscrasia, the accelerated destruction of blood cells and/or acquired disorders in catabolic pathways within the macrophages are suggested to be the underlying mechanism of an intralysosomal accumulation of incompletely degraded cellular debris. 相似文献
69.
Use of an Enrichment Broth Cultivation-PCR Combination Assay for Rapid Diagnosis of Swine Erysipelas 总被引:4,自引:1,他引:4 下载免费PDF全文
Yoshihiro Shimoji Yasuyuki Mori Koji Hyakutake Tsutomu Sekizaki Yuichi Yokomizo 《Journal of clinical microbiology》1998,36(1):86-89
We have previously described the creation by Tn916 mutagenesis of avirulent transposition mutants from a highly virulent strain of Erysipelothrix rhusiopathiae, the causative agent of swine erysipelas. In this study, we cloned a 2.2-kb DNA fragment which flanked the Tn916 insertion in an avirulent mutant (strain 33H6) and evaluated the possibility that this region could be used for the specific detection of E. rhusiopathiae. According to the sequences of this region, oligonucleotide primers were designed to amplify a 937-bp fragment of the E. rhusiopathiae chromosome by PCR. The specificity of the PCR was investigated by analyzing 64 strains of Erysipelothrix species and 27 strains of other genera different from Erysipelothrix. A 937-bp DNA fragment could be amplified from all E. rhusiopathiae strains tested, and no amplification was observed by using DNAs from the other species tested. To make a rapid and definite diagnosis of swine erysipelas in slaughterhouses, we developed an enrichment broth cultivation-PCR combination assay, which used a commercially available DNA extraction kit, to identify E. rhusiopathiae in the specimens from swine with arthritis. After samples were enriched in selective broth culture, detection of E. rhusiopathiae was tested by either conventional methods or the PCR. Of 102 samples tested, 15 samples were positive by conventional methods and 12 of the 15 samples were positive by the PCR. The detection limit of the PCR was 103 CFU per reaction mixture for the PCR-positive samples. These results indicate that this PCR technique could be used as a first-line screening technique for the specific detection of E. rhusiopathiae in specimens. 相似文献
70.
Michikawa Y Laderman K Richter K Attardi G 《Somatic Cell and Molecular Genetics》1999,25(5-6):333-342
Previous work had shown a large accumulation (up to 50% of mtDNA) of a noninherited T414G transversion at a critical control site for mtDNA replication in skin fibroblasts from the majority of human subjects above 65 years old, and its absence in younger individuals. In the present studies, long-term in vitro culture of several fibroblasts populations carrying the heteroplasmic T414G mutation revealed an outgrowth of the mutant cells by wild-type cells. This observation supported the previous conclusion that the mutation accumulation is an in vivo phenomenon, while, at the same time, indicating intrinsic physiological differences between mutant and wild-type cells. Furthermore, subcloning experiments revealed a striking mosaic distribution of the mutation in the original fibroblasts populations, as shown by its presence, in heteroplasmic or homoplasmic form, in a fraction (18–32%) of the fibroblasts, and its absence in the others. In other investigations, transfer of mitochondria from mutation-carrying fibroblasts into mtDNA-less 143B.TK–0 206 cells revealed the persistence of the mosaic distribution of the mutation, however, with a near-complete shift to homoplasmy. The generality of the latter phenomenon would exclude a founder effect by one or few mitochondria in the transformation experiments, and would rather point to the important role of the nuclear background in the in vitro behavior of the T414G mutation. The stability of the homoplasmic mutation in 0 cell transformants provides a powerful tool for analyzing its biochemical effects. 相似文献