全文获取类型
收费全文 | 1968篇 |
免费 | 106篇 |
专业分类
2074篇 |
出版年
2023年 | 11篇 |
2022年 | 33篇 |
2021年 | 45篇 |
2020年 | 30篇 |
2019年 | 42篇 |
2018年 | 62篇 |
2017年 | 52篇 |
2016年 | 68篇 |
2015年 | 116篇 |
2014年 | 109篇 |
2013年 | 181篇 |
2012年 | 185篇 |
2011年 | 168篇 |
2010年 | 92篇 |
2009年 | 83篇 |
2008年 | 103篇 |
2007年 | 95篇 |
2006年 | 88篇 |
2005年 | 50篇 |
2004年 | 58篇 |
2003年 | 76篇 |
2002年 | 64篇 |
2001年 | 15篇 |
2000年 | 15篇 |
1999年 | 30篇 |
1998年 | 12篇 |
1997年 | 13篇 |
1996年 | 11篇 |
1995年 | 12篇 |
1994年 | 11篇 |
1993年 | 12篇 |
1992年 | 19篇 |
1991年 | 17篇 |
1990年 | 16篇 |
1989年 | 8篇 |
1988年 | 8篇 |
1987年 | 11篇 |
1986年 | 6篇 |
1985年 | 9篇 |
1984年 | 3篇 |
1983年 | 7篇 |
1981年 | 5篇 |
1980年 | 2篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1973年 | 2篇 |
1965年 | 2篇 |
1934年 | 1篇 |
1929年 | 1篇 |
排序方式: 共有2074条查询结果,搜索用时 15 毫秒
1.
Ivana Tonic Wan-Ni Yu Youngku Park Chia-Chen Chen Nissim Hay 《The Journal of biological chemistry》2010,285(31):23790-23798
Akt is perhaps the most frequently activated oncoprotein in human cancers. Overriding cell cycle checkpoint in combination with the inhibition of apoptosis are two principal requirements for predisposition to cancer. Here we show that the activation of Akt is sufficient to promote these two principal processes, by inhibiting Chk1 activation with concomitant inhibition of apoptosis. These activities of Akt cannot be recapitulated by the knockdown of Chk1 alone or by overexpression of Bcl2. Rather the combination of Chk1 knockdown and Bcl2 overexpression is required to recapitulate Akt activities. Akt was shown to directly phosphorylate Chk1. However, we found that Chk1 mutants in the Akt phosphorylation sites behave like wild-type Chk1 in mediating G2 arrest, suggesting that the phosphorylation of Chk1 by Akt is either dispensable for Chk1 activity or insufficient by itself to exert an effect on Chk1 activity. Here we report a new mechanism by which Akt affects G2 cell cycle arrest. We show that Akt inhibits BRCA1 function that induces G2 cell cycle arrest. Akt prevents the translocation of BRCA1 to DNA damage foci and, thereby, inhibiting the activation of Chk1 following DNA damage. 相似文献
2.
3.
P Carde C Chastang E Goncalves N Mathieu-Tubiana E Vuillemin V Delwail O Corbion A Vekhoff F Isnard J M Ferrero 《Comptes rendus de l'Académie des sciences. Série III, Sciences de la vie》1992,315(13):545-550
Seraspenide, a synthetic tetrapeptide, inhibits cell cycle entry of normal hematopoietic stem cells. In mice it protects hemopoiesis against the damage caused by cytarabine, cyclophosphamide and carboplatin. Seraspenide has been given to 53 cancer patients undergoing monochemotherapy with cytarabine and ifosfamide in a double-blind cross-over randomized study. A significant protection of peripheral blood cells has been observed. Seraspenide has been devoided of toxicity. 相似文献
4.
Incubation of [14C] caffeine with hepatic microsomes from male AKR/J mice resulted in the formation of several metabolites including 1, 3, 7-trimethylurate and 6-amino-5-(N-formylmethyl-amino)-1, 3-dimethyluracil. These two compounds comprised about 60% of products and are major urinary metabolites in several animals. When cytosol was included during incubation, there was a 14-fold increase in yield of the uracil at the expense of the urate; the combination of the two metabolites remained about 60% of total products. Cytosol alone was catalytically inert. Glutathione and other sulfhydryl compounds reproduced the effect of cytosol, and the action of cytosol was accounted for quantitatively by its sulfhydryl content. We propose that an oxidized intermediate of caffeine en route to trimethylurate is reduced by glutathione to the ring-opened uracil derivative. 相似文献
5.
Robert S. Sparkes Hiroyuki Sasaki T. Mohandas Katsuji Yoshioka Ivana Klisak Yoshiyuki Sakaki Camilla Heinzmann Melvin I. Simon 《Human genetics》1987,75(2):151-154
Summary The assignment of the human prealbumin (PALB) gene to chromosome region 18q11–q12.1 has been achieved using a human genomic probe in the study of human-mouse somatic cell hybrids and by in situ hybridization. Because familial amyloidotic polyneuropathy was reported previously to be due to a mutation in prealbumin, it can be inferred that the gene for this disorder also maps to 18q11.2–q12.1. 相似文献
6.
7.
The monocyte differentiation antigen, CD14, is anchored to the cell membrane by a phosphatidylinositol linkage 总被引:59,自引:0,他引:59
A Haziot S Chen E Ferrero M G Low R Silber S M Goyert 《Journal of immunology (Baltimore, Md. : 1950)》1988,141(2):547-552
CD14 is a myeloid differentiation Ag expressed primarily on peripheral blood monocytes and macrophages. Although its function is unknown, the CD14 gene maps to a region encoding several myeloid growth factors and receptors. Analysis of the CD14 protein sequence deduced from the cDNA shows that although the CD14 protein contains a characteristic leader peptide, it lacks a characteristic transmembrane region, suggesting that CD14 may be anchored to the membrane via glycosylphosphatidylinositol (PI). Treatment of monocytes as well as a CD14-expressing neuroglioma cell line with PI-phospholipase C removed CD14 from the cell surface. Furthermore, monocytes from a patient with paroxysmal nocturnal hemoglobinuria, a disease characterized by lack of expression of other PI-linked proteins, failed to express CD14. Interestingly, the CD14-expressing neuroglioma cell line, which had been transfected with a single CD14 cDNA, released a soluble form of CD14 into the supernatant. Soluble forms of CD14 have previously been observed in serum of normal individuals and in culture supernatants of CD14+ cells. Biosynthetic experiments reveal that this soluble form of CD14 (48 kDa), which is smaller than the form released from the membrane by PI-phospholipase C (53 kDa), does not contain ethanolamine, the first constitutent of the PI-anchoring system. These studies demonstrate that CD14 is a member of the family of PI-anchored proteins and suggest that soluble forms of CD14 represent molecules that completely lack the PI-anchoring system. 相似文献
8.
Claudio Fortis Elisabetta Ferrero Mauro Biffi Silvia Heltai Carlo Besana Eraldo Bucci Moreno Tresoldi Claudio Rugarli 《Cancer immunology, immunotherapy : CII》1991,34(2):128-132
Summary Burkitt lymphoma (BL) lines can be grouped according to phenotypic characteristics. Group I cells exhibit the phenotype of resting B cells and grow as single cells. Such lines can be Epstein-Barr-virus(EBV)-negative or -positive. Group II and group III cells are always EBV-positive, they express B cell activation markers, grow in aggregates and resemble in varying degrees lymphoblastoid cell lines (LCL). We studied three groups of BL lines for their capacity to interact with allogeneic lymphocytes. The results showed that as long as the lines have the group I phenotype, they do not stimulate allogeneic T lymphocytes irrespective whether they carry the EBV genome. The group II and III cells are stimulatory. Generally there was no correlation between sensitivity to lymphocyte-mediated lysis and the phenotype of the lines. In one set of lines, the group I cells had higher sensitivity to both natural killer and lymphokine-activated killer effectors compared to the group II or III lines. However, such correlation could not be seen with the other two sets of lines. Among the phenotypic features investigated, expression of the adhesion molecules LFA-1 and LFA-3 correlated with the tendency for cell aggregation. 相似文献
9.
Biochemistry and expression of myelomonocytic antigens 总被引:11,自引:0,他引:11
S M Goyert E M Ferrero S V Seremetis R J Winchester J Silver A C Mattison 《Journal of immunology (Baltimore, Md. : 1950)》1986,137(12):3909-3914
Six monoclonal antibodies (MAb) which react with myelomonocytic cells representing various stages of differentiation, and which precipitate six different cell surface molecules, were identified. A 50 to 55 kilodalton (Kd) glycoprotein, restricted in expression to mature cells of the monocyte lineage, was detected by immunoprecipitation with antibody MoS39. By using COS-7 cells transfected with a cDNA clone encoding the MoS39 antigen, various well-described anti-monocyte MAb, including Mo2, My4, Leu-M3 (MoP9), MoP15, MoS1, and 63D3, also bound to MoS39-expressing COS-7 cells, suggesting that this group of antibodies reacted with the same glycoprotein. Immature cells of the myelomonocytic lineage were shown to express two distinct molecules: one with an m.w. of 26 to 28 Kd identified by antibody SG133, and the second, a 130 to 140 Kd glycoprotein identified by MoU26. Mature granulocytes were found to express a 60 Kd molecule identified by antibody SG185 which was absent from other cells of this lineage. Two other molecules were shown to be present on both mature and immature cells of the granulocytic and monocytic lineages: a 130 to 140 Kd glycoprotein identified by antibody SG134, and a 160 to 170 Kd glycoprotein recognized by antibody MoU48. 相似文献
10.