全文获取类型
收费全文 | 12992篇 |
免费 | 846篇 |
国内免费 | 2篇 |
专业分类
13840篇 |
出版年
2022年 | 56篇 |
2021年 | 148篇 |
2020年 | 88篇 |
2019年 | 122篇 |
2018年 | 178篇 |
2017年 | 133篇 |
2016年 | 236篇 |
2015年 | 339篇 |
2014年 | 415篇 |
2013年 | 776篇 |
2012年 | 713篇 |
2011年 | 724篇 |
2010年 | 444篇 |
2009年 | 447篇 |
2008年 | 770篇 |
2007年 | 697篇 |
2006年 | 730篇 |
2005年 | 722篇 |
2004年 | 728篇 |
2003年 | 682篇 |
2002年 | 627篇 |
2001年 | 342篇 |
2000年 | 327篇 |
1999年 | 284篇 |
1998年 | 162篇 |
1997年 | 143篇 |
1996年 | 107篇 |
1995年 | 123篇 |
1994年 | 105篇 |
1993年 | 112篇 |
1992年 | 197篇 |
1991年 | 187篇 |
1990年 | 175篇 |
1989年 | 166篇 |
1988年 | 159篇 |
1987年 | 140篇 |
1986年 | 115篇 |
1985年 | 95篇 |
1984年 | 116篇 |
1983年 | 96篇 |
1982年 | 70篇 |
1981年 | 67篇 |
1980年 | 69篇 |
1979年 | 108篇 |
1978年 | 74篇 |
1977年 | 86篇 |
1976年 | 47篇 |
1975年 | 45篇 |
1974年 | 48篇 |
1973年 | 47篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
111.
Takeshi Hara Tatsunori Kobayashi Satoshi Ito Xiangrong Zhou Tetsuro Katafuchi Hiroshi Fujita 《PloS one》2015,10(5)
Understanding of standardized uptake value (SUV) of 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography (FDG-PET) depends on the background accumulations of glucose because the SUV often varies the status of patients. The purpose of this study was to develop a new method for quantitative analysis of SUV of FDG-PET scan images. The method included an anatomical standardization and a statistical comparison with normal cases by using Z-score that are often used in SPM or 3D-SSP approach for brain function analysis. Our scheme consisted of two approaches, which included the construction of a normal model and the determination of the SUV scores as Z-score index for measuring the abnormality of an FDG-PET scan image. To construct the normal torso model, all of the normal images were registered into one shape, which indicated the normal range of SUV at all voxels. The image deformation process consisted of a whole body rigid registration of shoulder to bladder region and liver registration and a non-linear registration of body surface by using the thin-plate spline technique. In order to validate usefulness of our method, we segment suspicious regions on FDG-PET images manually, and obtained the Z-scores of the regions based on the corresponding voxels that stores the mean and the standard deviations from the normal model. We collected 243 (143 males and 100 females) normal cases to construct the normal model. We also extracted 432 abnormal spots from 63 abnormal cases (73 cancer lesions) to validate the Z-scores. The Z-scores of 417 out of 432 abnormal spots were higher than 2.0, which statistically indicated the severity of the spots. In conclusions, the Z-scores obtained by our computerized scheme with anatomical standardization of torso region would be useful for visualization and detection of subtle lesions on FDG-PET scan images even when the SUV may not clearly show an abnormality. 相似文献
112.
Summary A much higher incidence of alcohol flushing among Orientals in comparison to Caucasians, i.e., >50% vs 5%–10%, has been attributed to racial differences in alcohol-metabolizing enzymes. A large majority of Orientals are atypical in alcohol dehydrogenase-2 locus (ADH
2
), and their livers exhibit significantly higher ADH activity than the livers of most Caucasians. Approximately 50% of Orientals lack the mitochondrial aldehyde dehydrogenase (ALDH2) activity, and elimination of acetaldehyde might be disturbed. We determined by means of hybridization of genomic DNA samples with allele specific oligonucleotide probes, genotypes of the ADH
2
and ALDH
2
loci in Japanese alcohol flushers and nonflushers. We found that all individuals with homozygous atypical ALDH
2
2
/ALDH
2
2
and most of those with heterozygous atypical ALDH
1
2
/ALDH
2
2
were alcohol flushers, while all subjects with homozygous usual ALDH
1
2
/ALDH
1
2
were nonflushers. Frequency of the atypical ADH
2
2
was found to be higher in alcohol flushers than in nonflushers, but the statistical significance was not established in the sample size examined. 相似文献
113.
We report the biological characterization of an animal model of a genetic lipid storage disease analogous to human Wolman's disease. Affected rats accumulated cholesteryl esters (13.3-fold), free cholesterol (2.8-fold), and triglycerides (5.4-fold) in the liver, as well as cholesteryl esters (2.5-fold) and free cholesterol (1.33-fold) in the spleen. Triglycerides did not accumulate, and the levels actually decreased in the spleen. Analysis of the fatty acid composition of the cholesteryl esters and triglycerides showed high percentages of linoleic acid (18:2) and arachidonic acid (20:4) in both organs, especially in the liver. No accumulation of phospholipids, neutral glycosphingolipids, or gangliosides was found in the affected rats. Acid lipase activity for [14C]triolein, [14C]cholesteryl oleate, and 4-methyl-umbelliferyl oleate was deficient in both the liver and spleen of affected rats. Lipase activity at neutral pH was normal in both liver and spleen. Heterozygous rats showed intermediate utilization of these substrates in both organs at levels between those for affected rats and those for normal controls, although they did not accumulate any lipids. These data suggest that these rats represent an animal counterpart of Wolman's disease in humans. 相似文献
114.
Diffusivity of oxygen in blood serum 总被引:2,自引:0,他引:2
115.
Microphotoelectric plethysmography using a rabbit ear chamber 总被引:2,自引:0,他引:2
116.
117.
Hitomi Yatsuki Ken Higashimoto Kosuke Jozaki Kayoko Koide Junichiro Okada Yoriko Watanabe Nobuhiko Okamoto Yoshinobu Tsuno Yoko Yoshida Kazutoshi Ueda Kenji Shimizu Hirofumi Ohashi Tsunehiro Mukai Hidenobu Soejima 《Genes & genomics.》2013,35(2):141-147
Beckwith-Wiedemann syndrome (BWS) is an imprinting-related human disease that is characterized by macrosomia, macroglossia, abdominal wall defects, and variable minor features. BWS is caused by several genetic/epigenetic alterations, such as loss of methylation at KvDMR1, gain of methylation at H19-DMR, paternal uniparental disomy of chromosome 11, CDKN1C mutations, and structural abnormalities of chromosome 11. CDKN1C is an imprinted gene with maternal preferential expression, encoding for a cyclin-dependent kinase (CDK) inhibitor. Mutations in CDKN1C are found in 40 % of familial BWS cases with dominant maternal transmission and in ~5 % of sporadic cases. In this study, we searched for CDKN1C mutations in 37 BWS cases that had no evidence for other alterations. We found five mutations—four novel and one known—from a total of six patients. Four were maternally inherited and one was a de novo mutation. Two frame-shift mutations and one nonsense mutation abolished the QT domain, containing a PCNA-binding domain and a nuclear localization signal. Two missense mutations occurred in the CDK inhibitory domain, diminishing its inhibitory function. The above-mentioned mutations were predicted by in silico analysis to lead to loss of function; therefore, we strongly suspect that such anomalies are causative in the etiology of BWS. 相似文献
118.
Aoki S Ikeda S Takezawa T Kishi T Makino J Uchihashi K Matsunobu A Noguchi M Sugihara H Toda S 《Biochemical and biophysical research communications》2011,416(3-4):391-396
Encapsulating peritoneal sclerosis (EPS) often develops after transfer to hemodialysis and transplantation. Both termination of peritoneal dialysis (PD) and transplantation-related factors are risks implicated in post-PD development of EPS, but the precise mechanism of this late-onset peritoneal fibrosis remains to be elucidated. We previously demonstrated that fluid flow stress induced mesothelial proliferation and epithelial-mesenchymal transition via mitogen-activated protein kinase (MAPK) signaling. Therefore, we speculated that the prolonged bioactive effect of fluid flow stress may affect mesothelial cell kinetics after cessation of fluid streaming. To investigate how long mesothelial cells stay under the bioactive effect brought on by fluid flow stress after removal of the stress, we initially cultured mesothelial cells under fluid flow stress and then cultured the cells under static conditions. Mesothelial cells exposed to fluid flow stress for a certain time showed significantly high proliferative activity compared with static conditions after stoppage of fluid streaming. The expression levels of protein phosphatase 2A, which dephosphorylates MAPK, in mesothelial cells changed with time and showed a biphasic pattern that was dependent on the duration of exposure to fluid flow stress. There were no differences in the fluid flow stress-related bioactive effects on mesothelial cells once a certain time had passed. The present findings show that fluid flow stress exerts a prolonged bioactive effect on mesothelial cells after termination of fluid streaming. These findings support the hypothesis that a history of PD for a certain period could serve as a trigger of EPS after stoppage of PD. 相似文献
119.
Yumiko Ushio Naoki Yamamoto Antonio Sanchez-Bueno Ryotaro Yoshida 《Microbiology and immunology》1996,40(7):489-498
After an i.p. transplantation of an allogeneic tumor (Meth A) to C57BL/6 mice, a macrophage (MΦ)-rich, non-T, non-NK cell population is induced as the major infiltrate and cytotoxic cells. We here evaluated the role of the MΦs in the rejection of allografted Meth A cells and characterized the MΦs in comparison with other well-known MΦs. At all time intervals after transplantation, the highest cytotoxic activities against Meth A tumor were obtained with the MΦ-rich population. In addition, the lymphocyte-rich population had a significant but low cytotoxic activity, whereas two other population types, granulocytes and large granular cells, were inactive. When the MΦ-rich or the T cell-depleted MΦ-rich population was i.p. transplanted simultaneously with Meth A cells into untreated C57BL/6 mice, the tumor cells were rejected without growth. After specific elimination of MΦs by in vivo application of dichloromethylene diphosphonate-containing liposomes, the cytotoxic activity against Meth A cells was hardly induced at the transplantation site of Meth A cells and the allografted Meth A tumor continued to grow, indicating that a type of MΦ is the effector cell essential for the rejection. In contrast to other well-known MΦs, the cytotoxic activity against Meth A cells was cell-to-cell contact dependent and soluble factor (e.g., NO and TNF-α) independent. Moreover, the cytotoxic activity of the MΦs (H-2b) against 51Cr-labeled Meth A (H-2d) cells was inhibited by the addition of unlabeled H-2d, but not H-2a, H-2k or H-2b, lymphoblasts as well as Meth A cells, implying the specific interaction of the MΦs with H-2d cells. 相似文献
120.
Genotoxic stress exerts biological activity by activating downstream effectors, including the p53 tumor suppressor. p53 regulates cell-cycle checkpoint and induction of apoptosis in response to DNA damage; however, molecular mechanisms responsible for committing to these distinct functions remain to be elucidated. Recent studies demonstrated that phosphorylation of p53 at Ser46 is associated with induction of p53AIP1 expression, resulting in commitment to apoptotic cell death. In this regard, the role for Ser46 kinases in p53-dependent apoptosis has been established; however, the kinases responsible for Ser46 phosphorylation have yet to be identified. Here, we demonstrate that the dual-specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) directly phosphorylates p53 at Ser46. Upon exposure to genotoxic stress, DYRK2 translocates into the nucleus for Ser46 phosphorylation. Consistent with these results, DYRK2 induces p53AIP1 expression and apoptosis in a Ser46 phosphorylation-dependent manner. These findings indicate that DYRK2 regulates p53 to induce apoptosis in response to DNA damage. 相似文献