全文获取类型
收费全文 | 2850篇 |
免费 | 163篇 |
国内免费 | 36篇 |
专业分类
耳鼻咽喉 | 18篇 |
儿科学 | 43篇 |
妇产科学 | 51篇 |
基础医学 | 409篇 |
口腔科学 | 18篇 |
临床医学 | 183篇 |
内科学 | 907篇 |
皮肤病学 | 20篇 |
神经病学 | 282篇 |
特种医学 | 65篇 |
外科学 | 441篇 |
综合类 | 2篇 |
预防医学 | 60篇 |
眼科学 | 13篇 |
药学 | 91篇 |
中国医学 | 7篇 |
肿瘤学 | 439篇 |
出版年
2023年 | 19篇 |
2022年 | 35篇 |
2021年 | 55篇 |
2020年 | 31篇 |
2019年 | 43篇 |
2018年 | 55篇 |
2017年 | 45篇 |
2016年 | 49篇 |
2015年 | 70篇 |
2014年 | 100篇 |
2013年 | 118篇 |
2012年 | 188篇 |
2011年 | 237篇 |
2010年 | 121篇 |
2009年 | 100篇 |
2008年 | 208篇 |
2007年 | 160篇 |
2006年 | 164篇 |
2005年 | 180篇 |
2004年 | 168篇 |
2003年 | 147篇 |
2002年 | 181篇 |
2001年 | 41篇 |
2000年 | 45篇 |
1999年 | 38篇 |
1998年 | 56篇 |
1997年 | 44篇 |
1996年 | 43篇 |
1995年 | 44篇 |
1994年 | 31篇 |
1993年 | 14篇 |
1992年 | 22篇 |
1991年 | 18篇 |
1990年 | 25篇 |
1989年 | 27篇 |
1988年 | 14篇 |
1987年 | 13篇 |
1986年 | 9篇 |
1985年 | 8篇 |
1984年 | 16篇 |
1983年 | 12篇 |
1982年 | 6篇 |
1981年 | 5篇 |
1980年 | 6篇 |
1979年 | 7篇 |
1978年 | 3篇 |
1977年 | 9篇 |
1974年 | 3篇 |
1969年 | 3篇 |
1966年 | 3篇 |
排序方式: 共有3049条查询结果,搜索用时 31 毫秒
11.
Yoshito Matsui Tomoatsu Kimura Noriyuki Tsumaki Haruhiko Nakahara Nobuhito Araki Natsuo Yasui Takahiro Ochi 《Journal of orthopaedic science》1996,1(2):130-135
Recent DNA studies performed by several groups have detected mutations of the gene encoding fibroblast growth factor receptor
3 (FGFR3) in patients with achondroplasia-group disorders, including achondroplasia (ACH), hypochondroplasia (HCH), and thanatophoric
dysplasia (TD). For this study, we analyzed theFGFR3 gene in 31 Japanese patients with typical ACH, four with HCH, three with a condition intermediate between ACH and HCH (ACH/HCH-intermediate),
and one with TD. Of the 31 typical ACH patients, 29 showed a G1138 to A transition and the other two a G1138 to C transversion,
both resulting in a common Gly380Arg substitution in the transmembrane domain of FGFR3. The one TD and the four HCH patients
did not display any mutations in the transmembrane domain of FGFR3. Of the three ACH/HCH-intermediate cases, one patient showed
the Gly380Arg substitution and one did not, and further analysis of the second patient revealed the presence of Asn540Lys
substitution. The first patient was, therefore, genotypically diagnosed as ACH and the second as HCH. Peripheral blood leukocyte
DNA analysis in the remaining ACH/HCH-intermediate patient indicated an unequal ratio of mutant to normal PCR products, possibly
representing a somatic mosaic for the Gly380Arg mutation. Analysis of the common FGFR3 mutation thus appears to help in the
molecular diagnosis of patients with achondroplasia-group disorders. 相似文献
12.
13.
Etsuko Kiyokawa Yuko Hashimoto Shin Kobayashi Haruhiko Sugimura Takeshi Kurata Michiyuki Matsuda 《Genes & development》1998,12(21):3331-3336
DOCK180 is involved in integrin signaling through CrkII-p130Cas complexes. We have studied the involvement of DOCK180 in Rac1 signaling cascades. DOCK180 activated JNK in a manner dependent on Rac1, Cdc42Hs, and SEK, and overexpression of DOCK180 increased the amount of GTP-bound Rac1 in 293T cells. Coexpression of CrkII and p130Cas enhanced this DOCK180-dependent activation of Rac1. Furthermore, we observed direct binding of DOCK180 to Rac1, but not to RhoA or Cdc42Hs. Dominant-negative Rac1 suppressed DOCK180-induced membrane spreading. These results strongly suggest that DOCK180 is a novel activator of Rac1 and involved in integrin signaling. 相似文献
14.
Kazuhiko Yasuml Rong-Jun Guo Hiroyuki Hanai Hajime Arai Eizo Kaneko Hiroyuki Konno Selichi Takenoshita Koichi Hagiwara Haruhiko Sugimura 《Pathology international》1998,48(2):134-137
A new mutation in the serine-threonine klnase domain of the transforming growth factor β type II receptor (TGFpRII) was found in a case of diffuse, B cell non-Hodgkin's lymphoma of the stomach. A mfssense mutation (ACA to GCA, Thr to Ala) was detected In exon 5, and a wild type allele was also present. This Is the first naturally occurring mutation in the klnase domain of this gene identified in human primary lymphoma. The replication error at three loci was negative, and the poly A tract of exon 3, which is frequently a target of mismatch repair genes, was intact. Malignant lymphoma of B cell origin in the stomach Is an addition to an expanding catalogue of tumors with TGFβRII alterations, and the biological sequelae of the change in the functional domain and the clinical characteristics of the patient in this study are intriguing. 相似文献
15.
TCR repertoire in early fetal mouse thymus 总被引:1,自引:0,他引:1
Ohki-Hamazaki Hiroko; Makino Yasuhiko; Kanno Masamoto; Koseki Haruhiko; Akasaka Takeshi; Taniguchi Masaru 《International immunology》1995,7(3):493-499
We investigated the rearrangement and expression of TCR genesin mouse fetal thymus organ culture, a system that avoids subsequententry of hematopoietic precursor cells. The first observablerearranged TCR gene was homogeneous V2-J2, detectable as earlyas fetal day 11 (d11) in the thymic primordla. The productiveTCR was homogeneous V5-J1, first detectable in d13 thymocytes,followed by adult-type TCR (V4 and V7). Sequence analysis ofTCR revealed five types of V-J junctional sequences. In thevery early stage, a homogeneous V-J junction is generated viaa short homology sequence in the coding region (Type I), whilea short homology sequence in the P-nucleotlde rather than thecoding region is used in the following stage (Type II). In thelater embryonic stages, diverse V-J junctions are generatedby well-known mechanisms, such as P-nucleotide (Type III), N-regioninsertion (Type IV) or trimming of the coding ends (Type V).These findings suggest that the generation of homogeneous TCR (V2 and V5) in the early fetal stages is due to the intrinsicrearrangement mechanisms and is in stage specific manner. 相似文献
16.
Nishio J Iwasaki H Sakashita N Haraoka S Isayama T Naito M Miyayama H Yamashita Y Kikuchi M 《Human pathology》2003,34(3):246-252
Undifferentiated (embryonal) sarcoma of the liver (UESL) is a rare pediatric liver malignancy that is extremely uncommon in middle-aged individuals. We studied 2 cases of UESL in middle-aged adults (1 case in a 49-year-old woman and the other in a 62-year-old man) by histology, immunohistochemistry, and electron microscopy to clarify the cellular characteristics of this peculiar tumor. One tumor showed a mixture of spindle cells, polygonal cells, and multinucleated giant cells within a myxoid matrix and also revealed focal areas of a storiform pattern in a metastatic lesion. The other tumor was composed mainly of anaplastic large cells admixed with few fibrous or spindle-shaped components and many multinucleated giant cells. In both cases, some tumor cells contained eosinophilic hyaline globules that were diastase resistant and periodic acid-Schiff positive. Immunohistochemically, the tumor cells showed positive staining for smooth muscle markers, such as desmin, alpha-smooth muscle actin, and muscle-specific actin, and also for histiocytic markers, such as alpha-1-antitrypsin, alpha-1-antichymotrypsin, and CD68. Electron microscope examination revealed thin myofilaments with focal densities and intermediate filaments in the cytoplasm of tumor cells. Our studies suggest that UESL exhibits at least a partial smooth muscle phenotype in middle-aged adults, and this specific differentiation may be more common in this age group than in children. Tumor cells of UESL with smooth muscle differentiation in middle-aged adults show phenotypic diversity comparable to those of malignant fibrous histiocytoma with myofibroblastic differentiation. 相似文献
17.
Constitutive Expression of a Bacterial Pattern Recognition Receptor, CD14, in Human Salivary Glands and Secretion as a Soluble Form in Saliva 下载免费PDF全文
Akiko Uehara Shunji Sugawara Kouichi Watanabe Seishi Echigo Mitsunobu Sato Takahiro Yamaguchi Haruhiko Takada 《Clinical and Vaccine Immunology : CVI》2003,10(2):286-292
Saliva contains a number of proteins and glycoproteins that protect oral tissues, but little is known about the role of human saliva in innate immunity. Here we showed that human major salivary gland cells constitutively expressed a bacterial pattern recognition receptor, CD14, by immunohistochemistry. Human salivary gland cells in culture express CD14 mRNA and a 55-kDa CD14 protein in, but not on the cells, and secrete a soluble form with the same molecular mass. Human whole saliva contains a 55-kDa CD14, and the concentration of parotid saliva was 10-fold higher than whole saliva, which is comparable to that of serum CD14. Levels of CD14 in unstimulated whole and parotid saliva were unchanged before and after a meal and between unstimulated and stimulated saliva, indicating that saliva CD14 is constitutively secreted into the oral cavity. In contrast, lipopolysaccharide (LPS)-binding protein was below the detectable level. The saliva CD14 is functionally active in that it mediated the activation of CD14-lacking intestinal epithelial cells by LPS in a Toll-like receptor 4-dependent manner. These results suggested that saliva CD14 is important for the maintenance of oral health and possibly intestinal homeostasis. 相似文献
18.
Shigeru Okada Hitoshi Ohtsuki Osamu Midorikawa Keishi Hashimoto 《Pathology international》1982,32(1):149-155
A case of bronchial plasmacytoma occurring in a 57- year-old housewife is reported. She had had the productive cough and the "abnormal shadow" in the right lower lobe for three years before admission. On bronchocopy, a tumor was found in the right main bronchus, large enough to obstruct the air way. The tumor was resected through rigid bronchoscope. Histological impression was "plasmacytoma with local amyloid deposit." M-protein was never detected in the serum or urine. Applying the immunoperoxidase technique for the paraffin section, the plasma cells were found to contain only a single type of immunoglobulin, Ig G-L. The differential diagnosis between plasmacytoma and plasma cell granuloma was made, and plasmacytoma was considered to be one type of extranodal malignant lymphoma. 相似文献
19.
Murata K Inami M Hasegawa A Kubo S Kimura M Yamashita M Hosokawa H Nagao T Suzuki K Hashimoto K Shinkai H Koseki H Taniguchi M Ziegler SF Nakayama T 《International immunology》2003,15(8):987-992
CD69, known as an early activation marker antigen on T and B cells, is also expressed on platelets and activated neutrophils, suggesting certain roles in inflammatory diseases. In order to address the role of CD69 in the pathogenesis of arthritis, we established CD69-null mice. CD69-null mice displayed a markedly attenuated arthritic inflammatory response when injected with anti-type II collagen antibodies. Cell transfer experiments with neutrophils, but not T cells or spleen cells, from wild-type mice into CD69-null mice restored the induction of arthritis. These results indicate a critical role for CD69 in neutrophil function in arthritis induction during the effector phase. Thus, CD69 would be a possible therapeutic target for arthritis in human patients. 相似文献
20.
Nakashima I Kato M Akhand AA Suzuki H Takeda K Hossain K Kawamoto Y 《Antioxidants & redox signaling》2002,4(3):517-531
The signaling for activation of protein tyrosine kinases (PTKs) is usually started by binding of ligands to cell-surface receptors. However, recent evidence suggests the presence of ligand binding-independent signaling pathways that are mediated by oxidative stress. Oxidation and reduction of protein cysteine sulfhydryl (SH) groups may work as a molecular switch to start or to stop the signaling. It is known that oxidation of cysteine SH groups on protein tyrosine phosphatases switches off the action of protein tyrosine phosphatases. This event may not, however, signal for initial autophosphorylation of previously unphosphorylated PTKs, whereas it certainly prevents dephosphorylation of once-phosphorylated PTKs. We have suggested new mechanisms for oxidative stress-mediated PTK activation. First, cell-surface glycosylphosphatidylinositol-anchoring proteins and a phosphoglycolipid/cholesterol-enriched membrane microdomain termed a "raft" can be the direct targets of oxidative stress for inducing their clustering through an S-S-bonded or S-X-S-bonded crosslinking of cell-surface proteins and subsequent activation of raft-associating Src family PTKs. Second, intracellular specific cysteine SH groups on PTK proteins can be another target of oxidative stress for inducing a conformational change necessary for initial activation of PTKs. A possible relationship between cell-surface and intracellular events is that the former frequently induces superoxide production as the second messenger for the latter. 相似文献