全文获取类型
收费全文 | 1092篇 |
免费 | 81篇 |
国内免费 | 36篇 |
出版年
2023年 | 43篇 |
2022年 | 29篇 |
2021年 | 65篇 |
2020年 | 67篇 |
2019年 | 90篇 |
2018年 | 61篇 |
2017年 | 35篇 |
2016年 | 33篇 |
2015年 | 48篇 |
2014年 | 57篇 |
2013年 | 117篇 |
2012年 | 40篇 |
2011年 | 50篇 |
2010年 | 31篇 |
2009年 | 39篇 |
2008年 | 56篇 |
2007年 | 40篇 |
2006年 | 48篇 |
2005年 | 41篇 |
2004年 | 55篇 |
2003年 | 30篇 |
2002年 | 28篇 |
2001年 | 12篇 |
2000年 | 11篇 |
1999年 | 7篇 |
1998年 | 12篇 |
1997年 | 7篇 |
1996年 | 7篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 4篇 |
1992年 | 5篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 4篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1977年 | 3篇 |
1976年 | 1篇 |
排序方式: 共有1209条查询结果,搜索用时 15 毫秒
1.
《Journal of molecular biology》2021,433(17):166665
Transient receptor potential melastatin 4 (TRPM4) is a broadly expressed Ca2+ activated monovalent cation channel that contributes to the pathophysiology of several diseases.For this study, we generated stable CRISPR/Cas9 TRPM4 knockout (K.O.) cells from the human prostate cancer cell line DU145 and analyzed the cells for changes in cancer hallmark functions. Both TRPM4-K.O. clones demonstrated lower proliferation and viability compared to the parental cells. Migration was also impaired in the TRPM4-K.O. cells. Additionally, analysis of 210 prostate cancer patient tissues demonstrates a positive association between TRPM4 protein expression and local/metastatic progression. Moreover, a decreased adhesion rate was detected in the two K.O. clones compared to DU145 cells.Next, we tested three novel TRPM4 inhibitors with whole-cell patch clamp technique for their potential to block TRPM4 currents. CBA, NBA and LBA partially inhibited TRPM4 currents in DU145 cells. However, none of these inhibitors demonstrated any TRPM4-specific effect in the cellular assays.To evaluate if the observed effect of TRPM4 K.O. on migration, viability, and cell cycle is linked to TRPM4 ion conductivity, we transfected TRPM4-K.O. cells with either TRPM4 wild-type or a dominant-negative mutant, non-permeable to Na+. Our data showed a partial rescue of the viability of cells expressing functional TRPM4, while the pore mutant was not able to rescue this phenotype. For cell cycle distribution, TRPM4 ion conductivity was not essential since TRPM4 wild-type and the pore mutant rescued the phenotype.In conclusion, TRPM4 contributes to viability, migration, cell cycle shift, and adhesion; however, blocking TRPM4 ion conductivity is insufficient to prevent its role in cancer hallmark functions in prostate cancer cells. 相似文献
2.
Reuben S.E. Young Andrew P. Bowman Kaylyn D. Tousignant Berwyck L.J. Poad Jennifer H. Gunter Lisa K. Philp Colleen C. Nelson Shane R. Ellis Ron M.A. Heeren Martin C. Sadowski Stephen J. Blanksby 《Journal of lipid research》2022,63(6):100223
The cellular energy and biomass demands of cancer drive a complex dynamic between uptake of extracellular FAs and their de novo synthesis. Given that oxidation of de novo synthesized FAs for energy would result in net-energy loss, there is an implication that FAs from these two sources must have distinct metabolic fates; however, hitherto, all FAs have been considered part of a common pool. To probe potential metabolic partitioning of cellular FAs, cancer cells were supplemented with stable isotope-labeled FAs. Structural analysis of the resulting glycerophospholipids revealed that labeled FAs from uptake were largely incorporated to canonical (sn-) positions on the glycerol backbone. Surprisingly, labeled FA uptake also disrupted canonical isomer patterns of the unlabeled lipidome and induced repartitioning of n-3 and n-6 PUFAs into glycerophospholipid classes. These structural changes support the existence of differences in the metabolic fates of FAs derived from uptake or de novo sources and demonstrate unique signaling and remodeling behaviors usually hidden from conventional lipidomics. 相似文献
3.
Castration had no effect on prostatic inhibin-like activity as compared to normal controls. Consequent upon castration there
is a significant reduction in the inhibin content of the ventral prostate on a per gland basis. However, when expressed as
a function of protein content, there is no change. The data suggest that the very same epithelial cells which under the influence
of androgen carry out the characteristic exocrine secretory activity are responsible for the synthesis and secretion of inhibin-like
material. 相似文献
4.
Robert Sweetland Patricia C. Sheppard Janice G. Dodd Robert J. Matusik 《Molecular and cellular biochemistry》1988,84(1):3-15
Summary After castration, the rat dorsolateral prostate M-40 mRNA initially decreased then rebounded to precastrated levels. The cellular site of M-40 expression and its renewed expression after castration was defined by in situ hybridization histochemistry. In situ hybridization with either a 32P-labeled or biotin-labeled M-40 cDNA probe demonstrated that M-40 mRNA levels were higher in the lateral than dorsal prostate. A second androgen regulated gene, RWB, also was highly expressed in the lateral prostate. The biotinylated cDNA probes provided microscopic resolution of the expressing cells, revealing two distinct morphologies of lateral epithelium which expressed both the M-40 and RWB mRNA. These morphologies appeared in ducts which contained either epithelial cell sheets that were highly convoluted or thinner epithelial cells with a minimal degree of convolution. The RWB mRNA decreased in both cell populations in response to androgen withdrawal. The decline and reappearance of M-40 mRNA also appeared in both epithelial cell types. These data demonstrated that after castration the M-40 mRNA initially decreased as expected for an androgen sensitive gene and then progressed to a fully inducible state. The mechanism of this progression remains to be elucidated. 相似文献
5.
Different hormonal requirements for androgen-independent growth of normal and tumor epithelial cells from rat prostate 总被引:4,自引:0,他引:4
Wallace L. McKeehan Pamela S. Adams Danna Fast 《In vitro cellular & developmental biology. Plant》1987,23(2):147-152
Summary The proliferation of isolated normal prostate epithelial cells from rat and man is androgen-independent and requires cholera
toxin, insulin, dexamethasone, epidermal growth factor (EGF) and one or more polypeptide factors that are concentrated in
bovine neural tissue. The active agents in the neural tissue extract are heparin-binding polypeptides (prostatropins), the
predominant form of which has a molecular weight of 17400 and an acetylalanine at the aminoterminus. Prostatropins supported
a half-maximal increase in normal prostate epithelial cell number at 50 picomolar. The proliferation of primary and serially-cultured
epithelial cells from androgen-responsive Dunning R3327 rat prostate tumors was also androgen-independent, but exhibited dramatic
alterations in response to hormones that stimulated normal cell proliferation. At low cell density, androgen-independent growth
of isolated tumor-derived epithelial cells was independent on cholera toxin, was stimulated by dexamethasone, required insulin
andeither EGFor prostatropin. The presence of either EGF or prostatropin masked the response to the other factor. In the absence of EGF,
purified prostatropins supported a half-maximal increase in tumor cell number at 7 picomolar. Endogenous production of EGF-like
and prostatropin-like factors or both was suggested by the reduced requirement for EGF and prostatropin at high prostate tumor
cell density. These results suggest that anti-hormonal therapies against prostate tumor growth should be based on intervention
with the activity of insulin (or insulin-like factors) or simultaneous intervention with both EGF and prostatropin (or their
homologues).
This work was supported by NIH grants CA 37589 and HL 33847, and grant 1718 from the Council for Tobacco Research.
Editor’s Statement This paper is the first report of the comparison of the hormone requirements of primary cultures of normal
and tumor prostate epithelial cells from the same system. 相似文献
6.
Marion T. Hierowski 《FEBS letters》1983,154(1):92-96
Quantitative analyses of LH-RH-like membrane receptors were performed in five tumors from the transplantable Dunning R3372H rat prostatic adenocarcinoma. The binding of D-Trp6-LH-RH, an agonist of LH-RH, was observed in all 5 tumors. The antagonist [Ac-Dp-Cl-Phe1,2,D-Trp3,D-Lys6,D-Ala10]-LH-RH was bound to 4 tumors. The apparent equilibrium dissociation constant (Kd) for D-Trp6-LH-RH receptor was from 2.6–3.9 × 10?10 M. The apparent equilibrium Bmax values (maximum number of binding sites) were from 17.2–86.0 fmol/mg membrane protein for D-Trp6-LH-RH receptor. The Kd for the antagonist was from 2.4–2.7 × 10?10 M and the Bmax values were from 35.5–66.0 fmol/mg membrane protein. Similar binding studies performed in 6 normal rat prostates showed no binding capacities. 相似文献
7.
Yuhsi Matuq Pamela S. Adams Nozomu Nishi Hidetaro Yasumitsu John W. Crabb Robert J. Matusik Wallace L. McKeehan 《In vitro cellular & developmental biology. Plant》1989,25(6):581-584
Summary Rat prostate extracts contain an abundant 20–22 kilodalton heparin-binding protein with near identical chromatographic properties,
but only 0.2–1% of the mitogenic activity, of bovine brain heparin-binding growth factor-1 (acidic fibroblast growth factor).
Amino terminal amino acid sequence (met-met-thr-asp-lys-asn-leu-lys-lys-lys-ile-glu-gly-asn-trp-arg-thr-val-tyr-leu-ala-ala-ser-?-val-glu-lys-ile-asn-glu-gly-ser-pro)
and immunochemical analysis revealed that the protein is identical to the androgen-dependent protein “probasin”.
This work was supported in part by NCI grant CA37589 (W. L. M., J. W. C.) and the Medical Research Council of Canada (R. J.
M.). 相似文献
8.
N. del Hoyo J. A. Pulido M. T. Carretero M. A. Pérez-Albarsanz 《Bioscience reports》1990,10(1):105-112
Rat ventral prostate incorporated (1-14C)acetate, (1-14C)palmitate and (1-14C)linoleate into different phospholipids in a time-dependent process. The rate of incorporation into total phospholipids was higher with linoleate (10.0 nmol/g) than with either palmitate (5.8 nmol/g) or acetate (4.7 nmol/g). Predominant labelling with all the radioactive substrates assayed was found in choline glycerophospholipids (PC). The radioactive profiles for linoleate in the other ventral prostate phospholipids differed from those obtained with palmitate and acetate. Specifically linoleate was incorporated into inositol glycerophospholipids plus lysoethanolamine glycerophospholipids (PI+LPE) and not into sphingomyelin (SM), while palmitate and acetate incorporated into SM but not into PI+LPE. Acetate showed the highest oxidation to CO2 whereas no differences were observed in the radioactivity incorporated into CO2 from a saturated (palmitate) or an essential unsaturated fatty acid (linoleate). These studies also show zinc-dependence by the acetate to CO2 oxidation.Abbreviations PL
total phospholipids
- PC
choline glycerophospholipids
- PE
ethanolamine glycerophospholipids
- PI+LPE
inositol glycerophospholipids plus lysoethanolamine glycerophospholipids
- PS
serine glycerophospholipids
- SM
sphingomyelin 相似文献
9.
Serum-free culture of enriched mouse anterior and ventral prostatic epithelial cells in collagen gel
Timothy Turner Howard A. Bern Peter Young Gerald R. Cunha 《In vitro cellular & developmental biology. Plant》1990,26(7):722-730
Summary Sustained growth of mouse ventral and anterior prostatic epithelial cells embedded within collagen gel matrix was achieved
in a serum-free medium composed of Dulbecco's modified Eagle's medium and Ham's F12 medium, 1∶1 (vol/vol), supplemented with
bovine serum albumin fraction V, epidermal growth factor, transferrin, cholera toxin, prolactin, 5α-dihydrotestosterone, cortisol,
putrescine, fibroblast growth factor, and a trace element mixture. Three-dimensional growth of prostatic epithelial cells
occurred inside the collagen gel matrix. This serum-free medium allowed cell growth greater than sevenfold over 10 d in culture.
Tissue recombination and cell culture techniques were integrated to demonstrate that cultured cells retained prostatic characteristics.
Following 10 d of culture, epithelial colonies from mouse ventral and anterior prostatic epithelial cell cultures were isolated
and combined with rat fetal urogenital sinus mesenchyme and grown for 4 wk under the renal capsule of intact athymic male
mice. These tissue recombinants showed distinctive prostatic histologic characteristic (alveoli and ducts lined with cuboidal
or columnar epithelium surrounded by stroma). When histologic sections of recombinants were stained with the Hoechst 33258,
epithelial cells of mouse origin were distinguishable from stromal cells of rat origin.
Aided by grants CA-05388 and CA-09041 from the National Institutes of Health, Bethesda, MD, and by M. A. R. C. fellowship
GM08730 to T. T. 相似文献
10.
A preliminary report on the use of transfer factor for treating stage D3 hormone-unresponsive metastatic prostate cancer 总被引:4,自引:0,他引:4
Dr. Giancarlo Pizza Caterina De Vinci Diego Cuzzocrea Domenico Menniti Ernesto Aiello Paolo Maver Giuseppe Corrado Piero Romagnoli Ennio Dragoni Giuseppe LoConte Umberto Riolo Aldopaolo Palareti Paolo Zucchelli Vittorio Fornarola Dimitri Viza 《Biotherapy》1996,9(1-3):123-132
As conventional treatments are unsuccessful, the survival rate of stage D3 prostate cancer patients is poor. Reports have
suggested the existence of humoral and cell-mediated immunity (CMI) against prostate cancer tumour-associated antigens (TAA).
These observations prompted us to treat stage D3 prostate cancer patients with an in vitro produced transfer factor (TF) able
to transfer, in vitro and in vivo, CMI against bladder and prostate TAA. Fifty patients entered this study and received one
intramuscular injection of 2–5 units of specific TF monthly. Follow-up, ranging from 1 to 9 years, showed that complete remission
was achieved in 2 patients, partial remission in 6, and no progression of metastatic disease in 14. The median survival was
126 weeks, higher than the survival rates reported in the literature for patients of the same stage. 相似文献