全文获取类型
收费全文 | 1866篇 |
免费 | 129篇 |
出版年
2023年 | 3篇 |
2022年 | 19篇 |
2021年 | 30篇 |
2020年 | 16篇 |
2019年 | 21篇 |
2018年 | 30篇 |
2017年 | 12篇 |
2016年 | 51篇 |
2015年 | 99篇 |
2014年 | 94篇 |
2013年 | 112篇 |
2012年 | 154篇 |
2011年 | 159篇 |
2010年 | 102篇 |
2009年 | 84篇 |
2008年 | 85篇 |
2007年 | 103篇 |
2006年 | 79篇 |
2005年 | 86篇 |
2004年 | 108篇 |
2003年 | 78篇 |
2002年 | 83篇 |
2001年 | 49篇 |
2000年 | 44篇 |
1999年 | 41篇 |
1998年 | 20篇 |
1997年 | 13篇 |
1996年 | 17篇 |
1995年 | 12篇 |
1994年 | 6篇 |
1993年 | 12篇 |
1992年 | 20篇 |
1991年 | 17篇 |
1990年 | 12篇 |
1989年 | 20篇 |
1988年 | 13篇 |
1987年 | 10篇 |
1986年 | 10篇 |
1985年 | 8篇 |
1984年 | 9篇 |
1983年 | 3篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1977年 | 7篇 |
1975年 | 10篇 |
1974年 | 4篇 |
1972年 | 2篇 |
1966年 | 2篇 |
排序方式: 共有1995条查询结果,搜索用时 484 毫秒
71.
Koh N Fujimori T Nishiguchi S Tamori A Shiomi S Nakatani T Sugimura K Kishimoto T Kinoshita S Kuroki T Nabeshima Y 《Biochemical and biophysical research communications》2001,280(4):1015-1020
We recently identified a novel gene, termed klotho (kl) that is involved in the development of a syndrome in mice resembling human aging. A defect of the kl gene expression in mice leads to multiple disorders including arteriosclerosis, osteoporosis, ectopic calcification, and skin atrophy together with short life-span and infertility. Patients with chronic renal failure (CRF), develop multiple complications that are reminiscent of phenotypes observed in kl mutant mice. Furthermore, the kl gene is mainly expressed in kidney and brain. These evidences above suggest the possible involvement of Klotho function in the complications arising in CRF patients. To investigate the above possibility, we examined the kidneys of 10 clinically or histologically diagnosed CRF cases. The level of kl gene expression was measured by utilizing RNase protection assay. The expression of Klotho protein was assayed by utilizing Western blot analysis and by immunohistochemistry. The levels of kl mRNA expression were greatly reduced in all CRF kidneys. Moreover, the production of Klotho protein was also severely reduced in all CRF kidneys. These results suggest that the decrease in kl gene expression in CRF patients may underlie the deteriorating process of multiple complications in the CRF patients. 相似文献
72.
BACKGROUND: Fine needle aspiration cytology (FNAC) is effective in the diagnosis of bone tumors when combined with careful radiologic and clinical evaluation. However, cases where clinical or radiologic findings are atypical or unusual may lead to an erroneous diagnosis. CASE: A 19-year-old male presented with a pain in the left hip area that had been slowly progressive over a 10-month period. Clinical and radiologic findings suggested either giant cell tumor or chondroblastoma. The smeared aspiration specimen showed loosely cohesive, oval to round cells with moderate amounts of pale pink cytoplasm admixed with pinkish-blue, chondromyxoid material. The individual cells contained a single nucleus with evenly distributed, fine chromatin. A few osteoclastic giant cells were scattered in the smears. A cytologic diagnosis of myxoid lesion with a few giant cells, suspicious for chondromyxoid fibroma, was made. The diagnosis of chondrosarcoma was made by subsequent histologic examination. CONCLUSION: Absence of the usual clinicoradiologic features of chondrosarcoma combined with an unusual cytologic presentation in this case led to a misdiagnosis. In most centers, FNAC has achieved undisputed status as a diagnostic tool, and cytologic diagnosis often forms the basis of the therapeutic protocol. However, at some sites FNAC diagnosis is more problematic. Awareness of the limitations and pitfalls of FNAC is just as important as knowledge of the scope of FNAC in bone tumors. Tumors with chondromyxoid features provide particular difficulties. 相似文献
73.
Schurter BT Koh SS Chen D Bunick GJ Harp JM Hanson BL Henschen-Edman A Mackay DR Stallcup MR Aswad DW 《Biochemistry》2001,40(19):5747-5756
74.
75.
Nohara C Akiba H Nakajima A Inoue A Koh CS Ohshima H Yagita H Mizuno Y Okumura K 《Journal of immunology (Baltimore, Md. : 1950)》2001,166(3):2108-2115
OX40 (CD134) and its ligand (OX40L) have been implicated in T cell activation and migration. In this study, we examined the contribution of these molecules to the pathogenesis of experimental autoimmune encephalomyelitis (EAE) by administering a neutralizing mAb against murine OX40L (RM134L) to proteolipid protein (139-151) peptide-induced EAE in SJL mice. Administration of RM134L effectively ameliorated the disease in both actively induced and adoptively transferred EAE models. Histological examination showed that the RM134L treatment greatly reduced mononuclear cell infiltration into the spinal cord. The RM134L treatment did not inhibit the development of pathogenic T cells, given that proliferative response and IFN-gamma production by draining lymph node cells were not reduced or rather enhanced upon restimulation with proteolipid protein (139-151) in vitro, and these cells effectively transferred EAE to naive SJL mice. Flow cytometric analyses showed that the RM134L treatment inhibited the accumulation of OX40-expressing CD4(+) T cells and the migration of adoptively transferred CD4(+) T cells in the spinal cord. Immunohistochemical staining showed that OX40L was most prominently expressed on endothelial cells in the inflamed spinal cord. These results suggest that the OX40/OX40L interaction plays a critical role for the migration of pathogenic T cells into the CNS in the pathogenesis of EAE. 相似文献
76.
In many plant RNA viruses, Domains 1, 2 and 3 are conserved in replicase proteins. In order to examine the interference of viral replication by the Domain 1 sequence, we generated transgenic plants transformed with DNA corresponding to the Domain 1 sequence of the TMV 126 kDa protein. This DNA sequence includes the TMV RNA from nucleotides 1 to 2,149, which comprises both the 5'-untranslated and methyl transferase region. The transgenic plants obtained showed complete resistance to TMV infection. The presence of the Domain 1 sequence in the plants completely prevented local necrosis in Nicotiana tabacum cv. Xanthi nc, and any systemic development of symptoms in Nicotiana tabacum Xanthi upon TMV inoculation. Most transgenic plants sustained the conferred resistance even under TMV inoculum concentrations up to as high as 1,000 microg/ml. To detect any accumulation of TMV coat protein or viral RNA in infected transgenic plants, immunochemical tests and Northern blot analyses were carried out. Neither viral RNA or coat protein was detectable in the systemic leaves of the completely resistant transgenic plants, whereas they were accumulated in large quantities in all of the control plants. Because of the conservation of Domain 1 in many plant RNA viruses, the acquisition of resistance to virus infection using the Domain 1 sequence appears to be a very effective strategy for breeding of viral resistant plants. 相似文献
77.
Flett F de Mello Jungmann-Campello D Mersinias V Koh SL Godden R Smith CP 《Molecular microbiology》1999,31(3):949-958
The Streptomyces coelicolor dnaE gene, encoding the catalytic alpha-subunit of DNA polymerase III (pol III) was isolated by genetic complementation of a temperature-sensitive DNA replication mutant, S. coelicolor ts-38. The deduced protein sequence (1179 residues) is highly similar to the Escherichia coli-type pol III alpha-subunit, rather than to the PolC-type alpha-subunit that is known to be essential for replication in the 'low G + C' Gram-positive bacteria such as Bacillus subtilis. The dnaE gene is able to restore replication to a 'slow stop' mutant (ts-38) and a 'fast stop' mutant (ts-114); the dnaE gene of ts-38 carries a single amino acid substitution (Glu-802 to Lys), and the mutation in ts-114 has been mapped between codons 697 and 1062 of dnaE. Mutant ts-38 is considered to be defective in assembly of the multisubunit pol III holoenzyme and, hence, in initiation of replication, whereas ts-114 is defective in chain elongation. This study provides the first evidence that a DnaE-type pol III is essential for replication in a Gram-positive bacterium. In addition, the complementation studies suggest that the C-terminal 117 residues are not essential for DnaE function in S. coelicolor. When integrated at a distant site on the chromosome, a fragment containing the 3' half of dnaE(codons 697-1179) is capable of rescuing ts-38 (but not ts-114) at the restrictive temperature; it was demonstrated that homogenotization was responsible for this phenomenon. 相似文献
78.
The effects of bombesin (BB) on mitogen activated protein (MAP) kinase were investigated using non-small cell lung cancer (NSCLC) cells. By Western blot, both 42 and 44 kDalton forms of MAP kinase were present in NCI-H1299 and NCI-H838 cells. Addition of BB to NCI-H1299 cells resulted in phosphorylation of the MAP kinase substrate myelin basic protein (MBP). Phosphorylation of MBP was maximal 6 min after the addition of 10 nM BB to NCI-H1299 cells. Addition of gastrin releasing peptide (GRP) or GRP14-27 but not GRP1-16 to NCI-H 1299 cells caused MBP phosphorylation. The effects of BB were inhibited by BW2258U89, a BB receptor antagonist, and PD98059, a MAP kinase kinase inhibitor. Also, PD98059 inhibited the clonal growth of NCI-H1299 cells. These data suggest that MAP kinase may be an important regulatory enzyme in NSCLC. 相似文献
79.
80.