全文获取类型
收费全文 | 18086篇 |
免费 | 1721篇 |
国内免费 | 4344篇 |
出版年
2024年 | 129篇 |
2023年 | 440篇 |
2022年 | 552篇 |
2021年 | 572篇 |
2020年 | 556篇 |
2019年 | 582篇 |
2018年 | 418篇 |
2017年 | 481篇 |
2016年 | 509篇 |
2015年 | 622篇 |
2014年 | 1182篇 |
2013年 | 829篇 |
2012年 | 1038篇 |
2011年 | 1262篇 |
2010年 | 938篇 |
2009年 | 1127篇 |
2008年 | 1314篇 |
2007年 | 960篇 |
2006年 | 887篇 |
2005年 | 927篇 |
2004年 | 924篇 |
2003年 | 772篇 |
2002年 | 816篇 |
2001年 | 806篇 |
2000年 | 656篇 |
1999年 | 617篇 |
1998年 | 486篇 |
1997年 | 434篇 |
1996年 | 479篇 |
1995年 | 457篇 |
1994年 | 419篇 |
1993年 | 332篇 |
1992年 | 337篇 |
1991年 | 276篇 |
1990年 | 262篇 |
1989年 | 235篇 |
1988年 | 113篇 |
1987年 | 86篇 |
1986年 | 56篇 |
1985年 | 128篇 |
1984年 | 43篇 |
1983年 | 34篇 |
1982年 | 20篇 |
1981年 | 27篇 |
1980年 | 3篇 |
1978年 | 1篇 |
1976年 | 1篇 |
1966年 | 2篇 |
1963年 | 1篇 |
1950年 | 2篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
941.
Inducible resistance to Fas—mediated apoptosis in B cells 总被引:6,自引:0,他引:6
Rothstein TL 《Cell research》2000,10(4):245-266
Apoptosis produced in B cells through Fas(APO-1,CD95) triggering is regulated by signals derived from other surface receptors:CD40 engagement produces upregulation of Fas expression and marked susceptibility to Fas-induced cell death,whereas antigen receptor engagement,or IL-4R engagement,inhibits Fas killing and in so doing induces a state of Fas-resistance,even in otherwise sensitive,CD40-stimulated targets.Surface immunoglobulin and IL-4R utilize at least partially distinct path ways to produce Fas-resistance that differentially depend on PKC and STAT6,respectively.Further,surface immunoglobulin signaling for inducible Fas-resistance bypasses Btk,requires NF-κB,and entails new macromolecular synthesis.Terminal effectors of B cell Fas-resistance include the known anti-apoptotic gene products,Bcl-XL and FLIP,and a novel anti-apoptotic gene that encodes FAIM (Fas Apoptosis Inhibitory Molecule).faim was identified by differential display and exists in two alternatively spliced forms;faim-S is broadly expressed,but faim-L expression is tissue-specific.The FAIM sequence is highly evolu tionarily conserved,suggesting an important role for this molecule throughout phylogeny.Inducible resistance to Fas killing is hypothesized to protect foreign antigen-specific B cells during potentially hazardous interactions with FasL-bearing T cells,whereas autoreactive B cells fail to become Fas-resistant and are deleted via Fas-dependent cytotoxicity.Inadvertent or aberrant acquisition of Fas-resistance may permit autoreactive B cells to escape Fas deletion,and malignant lymphocytes to impede anti-tumor immunity. 相似文献
942.
Human mu-opioid receptor (HmuOR) with a tag of six consecutive histidines at its carboxyl terminus had been expressed in recombinant baculovirus infected Sf9 insect cells. The maximal binding capacity for the [3H] diprenorphine and [3H]ohmefentanyl (Ohm) were 9.1 +/- 0.7 and 6.52 +/- 0.23 nmol/g protein, respectively. The [3H] diprenorphine or [3H] Ohm binding to the receptor expressed in Sf9 cells was strongly inhibited by mu-selective agonists [D-Ala2, N-methyl-Phe4, glyol5]enkephalin (DAGO), Ohm, and morphine, but neither by delta nor by kappa selective agonist. Na+ (100 mM) and GTP (50 microM) could reduce HmuOR agonists etorphine and Ohm affinity binding to the overexpressed HmuOR. mu-selective agonists DAGO and Ohm effectively stimulated [35S]GTP-gammaS binding (EC50 = 2.7 nM and 6.9 nM) and inhibited forskolin- stimulated cAMP accumulation (IC50 = 0.9 nM and 0.3 nM). The agonist-dependent effects could be blocked by opioid antagonist naloxone or by pretreatment of cells with pertussis toxin (PTX). These results demonstrated that HmuOR overexpressed in Sf9 insect cells functionally coupled to endogenous G(i/o) proteins. 相似文献
943.
944.
945.
人早孕子宫蜕膜催乳素分泌的调节 总被引:1,自引:0,他引:1
子宫内膜蜕膜化对胚泡植入与妊娠维持是非常重要的。为探讨蜕膜化维持的调节机制 ,本文研究了妊娠早期人子宫蜕膜细胞催乳素 (PRL)分泌的调节。结果表明 :(1)孕酮显著地刺激PRL的分泌。 (2 )雌激素的作用与其浓度有关 ,生理浓度的雌激素对PRL分泌无明显影响 ,而高水平的雌激素抑制孕酮的刺激作用。合适的雌孕激素比例对蜕膜化的维持是必要的。 (3)RU486明显地抑制PRL的分泌 ,故认为孕酮的作用至少是部分通过受体介导的机制。 (4 )高浓度的cAMP (≥ 10 -5mol/L)显著增加PRL的分泌 ,cAMP信号系统可能在蜕膜化反应中发挥重要作用。 相似文献
946.
947.
948.
胸腺细胞在胸腺外凋亡的形态学证据 总被引:1,自引:0,他引:1
In vitro thymus explants culture designed in this paper can mimic the thymic microenvironment as it were in vivo. Theoretically, thymus explants are cut off free from blood stream. So if some developing or developed thymocytes had the inclination to migrate into the periphery, they would only be accumulated in the blood vessels within thymus explants. After 3-day's culture, under transmission electron microscope we observed the migrating thymocytes accumulated in the blood vessels of C57BL/6 mice thymus explants, and these thymocytes were occurring apoptosis at different stage. To our knowledge, this findings offers the first morphological evidence that thymocytes do not necessarily die inside the thymus in situ, and that having acquired the death signals thymocytes can migrate into the blood stream and die quickly outside the thymus. But this is not to say that we deny the intrathymic death hypothesis. On the contrary, we found the number of thymocytes occurring in situ apoptosis on the surfaces of stromal cells is far more than that of migrating into the blood vessels. So, our proposal is that there are two sites for thymocytes apoptosis, some die inside the thymus and the others die outside the thymus. 相似文献
949.
鼠白细胞介素12(mIL—12)在昆虫细胞中的表达 总被引:1,自引:0,他引:1
Since human IL-12 is species-specific in its functions and elicits little biological responses from mouse lymphocytes, it is necessary to express recombinant murine IL-12 for the usage in studying the effects of this cytokine in various rodent models. Thereby, we can investigate the role of IL-12 in immune response in vivo and evaluate its potential clinical utility. Thus, we firstly constructed two expression vectors, pVL1393-mp40 and pVL1393-mp35. They were used to co-transfect the insect cells(Sf9) separately with linearized polyhedrosis virus genomic DNA. Two kinds of recombinant viruses AcNPV-mp40 and AcNPV-mp35 were visually screened out, and mp40 and mp35 were co-expressed in the insect cells co-infected by AcNPV-mp40 and AcNPV-mp35. The results of real-time Biomolecular Interaction Analysis (BIA) and Northern blot demonstrated that the recombinant mIL-12 was expressed successfully in the insect cells. The molecular weights of recombinant mp40 and mp35 were 40 KDa and 22 KDa on SDS-PAGE under reducing conditions, respectively. The apparent molecular weight of recombinant mIL-12 is 80 KDa under non-reducing conditions of Western blot. Biological activity of the recombinant product was detected in conditional medium using antibody-capture bioassay. The expression level of recombinant mIL-12 was about 10-15 micrograms/10(6) cells, as compared with the calibration curve of mIL-12. 相似文献
950.
天花粉收白诱发白血病细胞K562凋亡的研究 总被引:8,自引:1,他引:7
Trichosanthin (TCS), an eukaryotic ribosome-inactivating protein isolated from the root tuber of Trichosanthes plant, has various biological activities including abortion induction, antitumor, and anti-HIV. In this study, cultured human leukemia K562 cells treated with trichosanthin were examined. Analysis of the cells by single laser flow cytometry showed the sub-G1 peak. DNA extracted from these cells formed a characteristic "ladder" on agarose gel electrophoresis. Under electromicroscope, typical morphological changes of apoptosis were also observed. From all of these findings, we concluded that trichosanthin was able to induce apoptosis in K562 cells. 相似文献