全文获取类型
收费全文 | 4948篇 |
免费 | 315篇 |
国内免费 | 447篇 |
出版年
2024年 | 25篇 |
2023年 | 120篇 |
2022年 | 173篇 |
2021年 | 231篇 |
2020年 | 182篇 |
2019年 | 300篇 |
2018年 | 217篇 |
2017年 | 150篇 |
2016年 | 143篇 |
2015年 | 200篇 |
2014年 | 363篇 |
2013年 | 517篇 |
2012年 | 273篇 |
2011年 | 331篇 |
2010年 | 173篇 |
2009年 | 183篇 |
2008年 | 206篇 |
2007年 | 197篇 |
2006年 | 183篇 |
2005年 | 183篇 |
2004年 | 132篇 |
2003年 | 127篇 |
2002年 | 131篇 |
2001年 | 98篇 |
2000年 | 77篇 |
1999年 | 74篇 |
1998年 | 64篇 |
1997年 | 62篇 |
1996年 | 54篇 |
1995年 | 44篇 |
1994年 | 56篇 |
1993年 | 51篇 |
1992年 | 42篇 |
1991年 | 55篇 |
1990年 | 20篇 |
1989年 | 32篇 |
1988年 | 18篇 |
1987年 | 32篇 |
1986年 | 15篇 |
1985年 | 19篇 |
1984年 | 23篇 |
1983年 | 24篇 |
1982年 | 23篇 |
1981年 | 22篇 |
1980年 | 14篇 |
1979年 | 24篇 |
1978年 | 8篇 |
1976年 | 7篇 |
1975年 | 4篇 |
1974年 | 4篇 |
排序方式: 共有5710条查询结果,搜索用时 15 毫秒
41.
Hisashi Miyazaki Masatoshi Iida Yoshimasa Matsunaga Toshihiko Fujii Keiko Nambu Hideki Amejima Yoshinori Oh-e Hideo Furukawa Yukiharu Matsui Yasunobu Sohmura Masahisa Hashimoto 《Biotherapy》1989,1(1-2):47-57
The mode of antitumor action of rHu-TNF was elucidated in BALB/c mice bearing Meth A fibrosarcoma 7 days after transplantation with respect to time course, dose-response relationships and selectivity of the effects. The maximal cytotoxic effect on tumor cells revealed by inhibition of DNA synthesis and maximal lesional effect on tumor vasculature revealed by change in blood pool-size in the tissue were detected at 30 min and I h after administration of rHu-TNF, respectively. The dose-response relationship between cytotoxic and tumoricidal effects of rHu-TNF was irrespective of administration route. ED50s of these antitumor effects afteri.v. administration of rHu-TNF were about 50 times as high as ED50s afteri.t. administration. ED50 ofi.t. given rHu-TNF for vascular effect was about 20 times as high as that for cytotoxicity while ED50 ofi.v. rHu-TNF for vascular effect was only 2–3 times as high as that for cytotoxicity. The whole body autoradiographies with [125I] HSA giveni.v. to see the blood influx into tumor tissue and [14C]thymidine given i.v. to see DNA synthesis in the whole body after administration of rHu-TNF revealed that the distribution of radioactivity was markedly changed in the tumor alone without any detectable change in other whole body tissues.In conclusion, thein vivo antitumor effect of rHu-TNF giveni.t. ori.v., appears to be exerted through the direct action on Meth A sarcoma rather than indirectly on tumor vasculature. Under present conditions, the effect of rHu-TNF in the whole body tissues seems rather selective on cells and vasculature of the tumor. 相似文献
42.
Flemming Jessen Bruce D. Cherksey Thomas Zeuthen Else K. Hoffmann 《The Journal of membrane biology》1989,108(2):139-151
Summary Furosemide-binding proteins were isolated from cholate-solubilized membranes of Ehrlich ascites tumor cells by affinity chromatography, using furosemide as ligand. Solubilized proteins retarded by the affinity material were eluted by furosemide. In reducing and denaturing gels, the major proteins eluted by furosemide were 100 and 45 kDa. In nonreducing, nondenaturing gels, homodimers of both polypeptides were found, whereas no oligomeric proteins containing both polypeptides were seen. It is concluded that the furosemide gel binds two distinct dimeric proteins. The isolated proteins were reconstituted into phospholipid vesicles and the K+ transport activity of these vesicles was assayed by measurement of86Rb+ uptake against a large opposing K+ gradient. The reconstituted system was found to contain a K+ transporting protein, which is sensitive to Ba2+ like the K+ channel previously demonstrated to be activated in intact cells after cell swelling. 相似文献
43.
Teresa L. Johnson Mary Pat Moyer 《In vitro cellular & developmental biology. Plant》1990,26(11):1095-1100
Summary Normal human colon mucosa cells and cells obtained from histologically normal tissues near that cancer were fused with human
colon cancer cells. Resultant hybrid populations of normal and malignant cell fusions behaved as nonmalignant cells in culture,
were unable to grow in soft agar, did not express tumor-associated antigens, and were nontumorigenic in nude mice. Autofusion
of the cancer cell population led to a phenotype intermediate between normal and malignant cells. That is, the cultures had
a much lower plating efficiency in soft agar, and the tumors had a longer latency and slower growth rate in nude mice. This
is the first cell culture system to demonstrate that normal epithelial cells can suppress malignancy of their autologous cancer
cells, and is a prelude to more extensive studies of genetic events involved in malignant conversion of human colonic epithelium.
This study was supported by The University of Texas Health Science Center at San Antonio Center for Human Cell Biotechnology
and a graduate student stipend (T. J.) from the Department of Cellular and Structural Biology. 相似文献
44.
Toshimitsu Okeda Yasushi Yokogawa Hiroaki Ueo Mary A. Bury Paul O. P. Ts'o Sarah A. Bruce 《In vitro cellular & developmental biology. Plant》1990,26(12):1157-1166
Summary Primary cultures of 9-d-gestation Syrian hamster embryo (E9) cells are distinct from primary cultures of later gestational
age in terms of their growth and differentiation. First, primary E9 cell cultures express multiple mesenchymal differentiation
lineages (e.g., adipocyte, myoblast) only rarely seen in cultures of 13-d-gestation fetal (F13) cells. Second, although most
primary E9 cultures have a limited in vitro proliferative life span and exhibit cellular senescence similar to primary cultures
of F13 cells, E9 cultures seem to have higher frequency of escape from senescence and conversion to continuous cell lines
compared to F13 cells. Moreover, this frequency can be further increased 4- to 5-fold by continuous exposure of the E9 cells
to tumor promoters or epidermal growth factor. Eleven continuous cell lines have been isolated from unreated, promoter-treated,
or epidermal growth factor-treated primary E9 cultures. Seven of these are neoplastic or preneoplastic. However, the remaining
four do not show any evidence of being in neoplastic progression and three of these continue to express the same differentiated
phenotype observed in ther parental primary cell cultures.
These studies were supported in part by grants from the National Institutes of Health (AG 01998), Bethesda, MD, and the U.S.
Department of Energy (DE-A-C02-76-EVO-3280), Washington, DC. 相似文献
45.
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
46.
APC基因是1991年被发现的一类肿瘤抑制基因,它被定位于人第5号染色体5q21处。APC基因如发生缺失或突变,则易患直肠肿瘤,并伴有部分先天痴呆的病例。本工作在孟帆已获得的APC基因在豚鼠中的同源cDNA的基础上,完成了对它的亚克隆,并利用原位杂交和RNA酶保护分析的方法,对它在脑中的分布进行了研究。发现APCmRNA主要在海马、大脑和小脑中表达;嗅球中杂交信号稍弱,脑干中最弱。海马中阳性细胞主要是锥体细胞,小脑中则主要是内层颗粒细胞。在一个月大的豚鼠胚胎的脑中也观察到相似的表达型式。进一步的研究有助于我们更好地了解神经发育和先天痴呆发生的分子机制。 相似文献
47.
J. Trémouillaux-Guiller H. Kodja J. C. Chénieux 《Plant Cell, Tissue and Organ Culture》1994,37(1):25-30
Protoplasts enzymatically isolated from cell line of Catharanthus roseus G. Don crown gall, were cultured at high density (105 P ml-1) in modified B5 liquid medium (Gamborg et al. 1976). In the absence of growth regulators C. roseus protoplasts were able to regenerate a cell-wall, divide and, subsequently, yield very numerous clones in the absence of growth regulators. After two weeks, the cultures were greatly diluted in order to obtain clones of single-cell origin. Most of the clones individually transferred onto solid medium can proliferate indefinitely, without growth regulators. Among analyzed clones, 90% were nopaline positive. Their ajmalicine and serpentine content was compared with that of the parental crown gall line, and was found to be low. The CR10 protoplasts were very easy to grow, they were an interesting model for the development of pure tumorous lines. Moreover, we found that the tumorous protoplasts were useful for cell fusion experiments or for the delicate culture of tree protoplasts.Abbreviations B5
Gamborg et al. (1976) medium
- 2,4-d
2,4-dichlorophenoxyacetic acid
- Kin
Kinetin
- NAA
naphthalene acetic acid
- BA
N6 (benzyl) adenine 相似文献
48.
49.
Daniel Keppler Patrice Waridel Magnus Abrahamson Daniel Bachmann José Berdoz Bernard Sordat 《生物化学与生物物理学报:疾病的分子基础》1994,1226(2):117-125
The lysosomal cystein proteinase cathepsin B is shown to be secreted by ten human colon carcinoma cell lines and to accumulate in culture media as a latent enzyme. The cell lines also secrete a physiological inhibitor of cathepsin B, cystatin C. A significant correlation was found between secretion of the latent enzyme and the inhibitor (r = 0.755, P < 0.01). The aim of the present study was to modulate the respective secretion of the two antagonists to test whether or not latency of cathepsin B was due to the concomitant secretion of the inhibitor. SW480 colon carcinoma cells were treated with the acidotropic agent ammonium chloride, phorbol 12-myristate 13-acetate, and the inflammatory cytokines TGF-β, TNF-α, and IL-1β. Ammonium chloride significantly increased latent cathepsin B levels without affecting the constitutive secretion of cystatin C. Phorbol 12-myristate 13-acetate induced a 4- to 5-fold increase in secreted latent cathepsin B, but did not alter significantly the accumulation of cystatin C in media. The cytokines, TGF-β, TNF-α, and IL-1β, had no major effect on the expression of these two antagonists. Latent cathepsin B released from human carcinoma cells could be efficiently activated by neutrophil elastate at neutral pH. It is concluded that latent cathepsin B is a true proenzyme rather than an enzyme-inhibitor comples. In addition, our data from neutrophil elastate activation experiments indicate that a proteolytic system for activation of the tumor cell-secreted latent enzyme may exist in vivo. 相似文献
50.
胎盘型谷胱甘肽S-转移酶基因在胃癌中的表达 总被引:1,自引:0,他引:1
用Dig-GST-πcDNA探针分子杂交方法,检测了正常胃组织,胃癌及相应癌旁正常组织中GST-πDNA和GST-πRNA水平,发现GST-πDNA水平没有明显变化,而GST-πRNA在8例胃癌组织中有6例高于正常胃组织,在12例低分化腺癌中有7例癌旁正常组织高于相应癌组织,表明GST-π基因表达增加与胃癌有关,而且早于细胞形态的变化。 相似文献