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881.
Li K Mandai M Hamanishi J Matsumura N Suzuki A Yagi H Yamaguchi K Baba T Fujii S Konishi I 《Cancer immunology, immunotherapy : CII》2009,58(5):641-652
Objective To investigate the clinical significance of the expression of the NKG2D ligands MICA/B and ULBP2 in ovarian cancer.
Methods Eighty-two ovarian cancer patients and six patients without ovarian cancer from Department of Obstetrics and Gynecology of
Kyoto University Hospital were enrolled in this study between 1993 and 2003. Expression of MICA/B, ULBP2, and CD57 in ovarian
cancer tissue and normal ovary tissue was evaluated by immunohistochemical staining, and the relationship of these results
to relevant clinical patient data was analyzed. Expression of MICs, ULBP2, and HLA-class I molecules in 33 ovarian cancer
cell lines and two normal ovarian epithelial cell lines, as well as levels of soluble MICs and ULBP2 in the culture supernatants,
were measured.
Results Expression of MICA/B and ULBP2 was detected in 97.6 and 82.9% of ovarian cancer cells, respectively, whereas neither was expressed
on normal ovarian epithelium. The expression of MICA/B in ovarian cancer was highly correlated with that of ULBP2. Strong
expression of ULBP2 in ovarian cancer cells was correlated with less intraepithelial infiltration of T cells and bad prognoses
for patients, suggesting that ULBP2 expression is a prognostic indicator in ovarian cancer. The expression of NKG2D ligands
did not correlate with the levels of the soluble forms of the ligands.
Conclusions High expression of ULBP2 is an indicator of poor prognosis in ovarian cancer and may relate to T cell dysfunction in the tumor
microenvironment.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
This work was supported by grants from Grant-in-Aid for Scientific Research (19390426, 19591932, 18209052 and 19659421) from
the Ministry of Education, Science, Sports, Culture and Technology of Japan. 相似文献
882.
Keduka E Kaiho A Hamada M Watanabe-Takano H Takano K Ogasawara M Satou Y Satoh N Endo T 《Gene》2009,429(1-2):49-58
The Ras family small GTPases play a variety of essential roles in eukaryotes. Among them, classical Ras (H-Ras, K-Ras, and N-Ras) and its orthologues are conserved from yeast to human. In ascidians, which phylogenetically exist between invertebrates and vertebrates, the fibroblast growth factor (FGF)-Ras-MAP kinase signaling is required for the induction of neural system, notochord, and mesenchyme. Analyses of DNA databases revealed that no gene encoding classical Ras is present in the ascidians, Ciona intestinalis and Halocynthia roretzi, despite the presence of classical Ras-orthologous genes in nematode, fly, amphioxus, and fish. By contrast, both the ascidians contain single genes orthologous to Mras, Rras, Ral, Rap1, and Rap2. A single Mras orthologue exists from nematode to mammalian. Thus, Mras evolved in metazoans independently of other Ras family genes such as Rras. Whole-mount in situ hybridization showed that C. intestinalis Mras orthologue (Ci-Mras) was expressed in the neural complex of the ascidian juveniles after metamorphosis. Knockdown of Ci-Mras with morpholino antisense oligonucleotides in the embryos and larvae resulted in undeveloped tails and neuronal pigment cells, abrogation of the notochord marker brachyury expression, and perturbation of the neural marker Otx expression, as has been shown in the experiments of the FGF-Ras-MAP kinase signaling inhibition. Mammalian Ras and M-Ras mediate nerve growth factor-induced neuronal differentiation in rat PC12 cells by activating the ERK/MAP kinase pathway transiently and sustainedly, respectively. Activated Ci-M-Ras bound to target proteins of mammalian M-Ras and Ras. Exogenous expression of an activated Ci-M-Ras in PC12 cells caused ERK activation and induced neuritogenesis via the ERK pathway as do mammalian M-Ras and Ras. These results suggest that the ascidian M-Ras orthologue compensates for lacked classical Ras and plays essential roles in neurogenesis in the ascidian. 相似文献
883.
Kazuhiro Umeyama Masahito Watanabe Hitoshi Saito Mayuko Kurome Sadaaki Tohi Hitomi Matsunari Keizaburo Miki Hiroshi Nagashima 《Transgenic research》2009,18(5):697-706
Pigs have been recognized as an excellent biomedical model for investigating a variety of human health issues. We developed
genetically modified pigs that exhibit the apparent symptoms of diabetes. Transgenic cloned pigs carrying a mutant human hepatocyte
nuclear factor 1α gene, which is known to cause the type 3 form of maturity-onset diabetes of the young, were produced using
a combined technology of intracytoplasmic sperm injection-mediated gene transfer and somatic cell nuclear transfer. Although
most of the 22 cloned offspring obtained died before weaning, four pigs that lived for 20–196 days were diagnosed as diabetes
mellitus with nonfasting blood glucose levels greater than 200 mg/dl. Oral glucose tolerance test on a cloned pig also revealed
a significant increase of blood glucose level after glucose loading. Histochemical analysis of pancreas tissue from the cloned
pigs showed small and irregularly formed Langerhans Islets, in which poor insulin secretion was detected. 相似文献
884.
Kenji Tomita H. Akiko Popiel Yoshitaka Nagai Tatsushi Toda Yuji Yoshimitsu Hiroaki Ohno Shinya Oishi Nobutaka Fujii 《Bioorganic & medicinal chemistry》2009,17(3):1259-1263
Aggregation and deposition of expanded polyglutamine proteins in the brain cause neurodegenerative diseases including Huntington disease. This pathogenic process is suppressed and delayed in the presence of polyglutamine binding peptide 1 (QBP1), which we previously identified as an undecapeptide binding to pathogenic polyglutamine proteins from phage display peptide libraries. In this paper, a structure–activity relationship study on QBP1 was conducted to determine the pharmacophores for inhibition of polyglutamine aggregation. Furthermore, a truncation study identified an octapeptide as the minimum structure for suppressing aggregation of polyglutamine proteins, which is equipotent to the parent undecapeptide QBP1. 相似文献
885.
886.
887.
On the young leaves, shoots, and buds of Cayratia japonica (Thunb.) Gagnep. (Vitaceae), we observed nutritious bodies called pearl bodies and hypothesized that they are utilized by
generalist predators as alternative foods. Some ambulate organisms consume pearl bodies in the wild and the predatory mite
Euseius sojaensis (Ehara) (Acari: Phytoseiidae) was considered as a primary candidate. Pearl bodies promoted E. sojaensis settlement on C. japonica leaves and E. sojaensis could prey on the phytophagous mite Tetranychus kanzawai Kishida (Acari: Tetranychidae) when the predators settle on a leaf before the prey. In addition, the presence of pearl bodies
did not reduce predation of E. sojaensis on T. kanzawai. This was seemingly because food quality of T. kanzawai was higher than pearl bodies. These results implied that pearl bodies on C. japonica leaves are utilized by E. sojaensis as alternative foods. 相似文献
888.
Minoru Tanaka Mayuko Okabe Kaori Suzuki Yoshiko Kamiya Yuko Tsukahara Shigeru Saito Atsushi Miyajima 《Mechanisms of development》2009,126(8-9):665-676
Hepatoblasts are hepatic progenitor cells that expand and give rise to either hepatocyte or cholangiocytes during liver development. We previously reported that delta-like 1 homolog (DLK1) is expressed in the mouse liver primordium at embryonic day (E) 10.5 and that DLK1+ cells in E14.5 liver contain high proliferative and bipotential hepatoblasts. While the expression of epithelial cell adhesion molecule (EpCAM) in hepatic stem/progenitor cells has been reported, its expression profile at an early stage of liver development remains unknown. In this study, we show that EpCAM is expressed in mouse liver bud at E9.5 and that EpCAM+DLK1+ hepatoblasts form hepatic cords at the early stage of hepatogenesis. DLK1+ cells of E11.5 liver were fractionated into EpCAM+ and EpCAM− cells; one forth of EpCAM+DLK1+ cells formed a colony in vitro whereas EpCAM−DLK1+ cells rarely did it. Moreover, EpCAM+DLK1+ cells contained cells capable of forming a large colony, indicating that EpCAM+DLK1+ cells in E11.5 liver contain early hepatoblasts with high proliferation potential. Interestingly, EpCAM expression in hepatoblasts was dramatically reduced along with liver development and the colony-forming capacities of both EpCAM+DLK1+ and EpCAM−DLK1+ cells were comparable in E14.5 liver. It strongly suggested that most of mouse hepatoblasts are losing EpCAM expression at this stage. Moreover, we provide evidence that EpCAM+DLK1+ cells in E11.5 liver contain extrahepatic bile duct cells as well as hepatoblasts, while EpCAM−DLK1+ cells contain mesothelial cell precursors. Thus, the expression of EpCAM and DLK1 suggests the developmental pathways of mouse liver progenitors. 相似文献
889.
d-Asp-containing proteins have been implicated in many aging-related diseases. To clarify the role of d-Asp-containing proteins in such diseases, we developed a screening system for these proteins using a d-aspartyl endopeptidase that specifically cleaves the proteins at the C-terminus. The digested proteins were detected by means
of two-dimensional gel electrophoresis and identified using nano-liquid chromatography/tandem mass spectrometry. We were able
to detect myelin basic protein, a known d-Asp-containing protein, in the brain tissues of mice; this indicates that our system is effective for screening d-Asp-containing proteins. 相似文献
890.
Saito Y Fukuhara A Nishio K Hayakawa M Ogawa Y Sakamoto H Fujii K Yoshida Y Niki E 《The Journal of nutritional biochemistry》2009,20(5):350-357
Coenzyme Q (CoQ) is a well-known electron transporter in the mitochondrial respiratory chain. Furthermore, ubiquinol (UQH(2))--a reduced form of ubiquinone (UQ)--has been shown to act as a radical-scavenging antioxidant. Some studies have reported the beneficial effect of CoQ addition to cultured cells; however, the cellular uptake and distribution of CoQ have not been elucidated. In the present study, we used rat pheochromocytoma PC12 cells to investigate and compare the cellular uptake and distribution of CoQ(10) and alpha-tocopherol (alphaT). UQ(10) or UQ(10)H(2) treatment resulted in an increase in the cellular content of both CoQ(10) in a time- and concentration-dependent manner. A subcellular fractionation study revealed that the added UQ(10) as well as UQ(10)H(2) mainly localized in the mitochondrial fraction, which is similar to the localization of endogenous CoQ but different from that of alphaT. The cellular distribution of alphaT directly corresponded to the lipid distribution, while the CoQ distribution did not show any relationship with the lipid distribution, particularly in the mitochondrial and microsomal fractions. These results indicate that the cellular distribution of CoQ is completely different from that of alphaT; moreover, a certain system which accumulates CoQ preferentially in mitochondria may be suggested. 相似文献