全文获取类型
收费全文 | 75853篇 |
免费 | 6687篇 |
国内免费 | 413篇 |
专业分类
82953篇 |
出版年
2023年 | 322篇 |
2022年 | 893篇 |
2021年 | 1458篇 |
2020年 | 899篇 |
2019年 | 1165篇 |
2018年 | 1602篇 |
2017年 | 1260篇 |
2016年 | 2106篇 |
2015年 | 3426篇 |
2014年 | 3858篇 |
2013年 | 4531篇 |
2012年 | 5769篇 |
2011年 | 5480篇 |
2010年 | 3492篇 |
2009年 | 3048篇 |
2008年 | 4357篇 |
2007年 | 4032篇 |
2006年 | 3646篇 |
2005年 | 3310篇 |
2004年 | 3289篇 |
2003年 | 2864篇 |
2002年 | 2506篇 |
2001年 | 2129篇 |
2000年 | 1949篇 |
1999年 | 1602篇 |
1998年 | 726篇 |
1997年 | 656篇 |
1996年 | 558篇 |
1995年 | 550篇 |
1994年 | 474篇 |
1993年 | 445篇 |
1992年 | 889篇 |
1991年 | 771篇 |
1990年 | 698篇 |
1989年 | 699篇 |
1988年 | 601篇 |
1987年 | 564篇 |
1986年 | 492篇 |
1985年 | 492篇 |
1984年 | 395篇 |
1983年 | 333篇 |
1982年 | 298篇 |
1981年 | 275篇 |
1980年 | 268篇 |
1979年 | 343篇 |
1978年 | 315篇 |
1977年 | 264篇 |
1976年 | 263篇 |
1975年 | 255篇 |
1974年 | 305篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
41.
42.
CD40 ligand-activated human monocytes amplify glomerular inflammatory responses through soluble and cell-to-cell contact-dependent mechanisms. 总被引:3,自引:0,他引:3
T Kuroiwa E G Lee C L Danning G G Illei I B McInnes D T Boumpas 《Journal of immunology (Baltimore, Md. : 1950)》1999,163(4):2168-2175
Monocytes/macrophages play a critical role in the initiation and progression of a variety of glomerulonephritides. We sought to define the interactions between physiologically activated human monocytes and glomerular mesangial cells (MC) by employing a cell culture system that permits the accurate assessment of the contribution of soluble factors and cell-to-cell contact. Human peripheral blood monocytes, primed with IFN-gamma and GM-CSF, were activated with CD40 ligand (CD40L) or TNF-alpha and cocultured with MC. CD40L-activated monocytes induced higher levels of IL-6, monocyte chemoattractant protein-1 (MCP-1) and ICAM-1 synthesis by MC. Separation of CD40L-activated monocytes from MC by a porous membrane decreased the mesangial synthesis of IL-6 by 80% and ICAM-1 by 45%, but had no effect on MCP-1. Neutralizing Abs against the beta 2 integrins, LFA-1 and Mac-1, decreased IL-6 production by 40 and 50%, respectively. Ligation of mesangial surface ICAM-1 directly enhanced IL-6, but not MCP-1, production. Simultaneous neutralization of soluble TNF-alpha and IL-1 beta decreased MCP-1 production by 55% in membrane-separated cocultures of MC/CD40L-activated monocytes. Paraformaldehyde-fixed CD40L-activated monocytes (to preserve membrane integrity but prevent secretory activity), cocultured with MC at various ratios, induced IL-6, MCP-1, and ICAM-1 synthesis by MC. Plasma membrane preparations from activated monocytes also induced mesangial IL-6 and MCP-1 synthesis. The addition of plasma membrane enhanced TNF-alpha-induced mesangial IL-6 production by approximately 4-fold. Together, these data suggest that the CD40/CD40L is essential for optimal effector function of monocytes, that CD40L-activated monocytes stimulate MC through both soluble factors and cell-to-cell contact mediated pathways, and that both pathways are essential for maximum stimulation of MC. 相似文献
43.
The spindle checkpoint is a cell cycle surveillance system that ensures the fidelity of chromosome segregation. In mitosis, it elicits the “wait anaphase” signal to inhibit the anaphase-promoting complex or cyclosome until all chromosomes achieve bipolar microtubule attachment and align at the metaphase plate. Because a single kinetochore unattached to microtubules activates the checkpoint, the wait anaphase signal is thought to be generated by this kinetochore and is then amplified and distributed throughout the cell to inhibit the anaphase-promoting complex/cyclosome. Several spindle checkpoint kinases participate in the generation and amplification of this signal. Recent studies have begun to reveal the activation mechanisms of these checkpoint kinases. Increasing evidence also indicates that the checkpoint kinases not only help to generate the wait anaphase signal but also actively correct kinetochore-microtubule attachment defects. 相似文献
44.
Influence of duodenal secretions and its components on release and activities of human brush-border enzymes 总被引:1,自引:0,他引:1
The in vitro effects of human duodenal secretions and various combinations of its components on activity and release of enzymes from the human brush border were examined. Sucrase retained activity for 90 min in duodenal secretions, and maltase was almost as stable; lactase lost activity rapidly and alkaline phosphatase was of intermediate stability. Inactivation of lactase could only be partly (50%) attributed to luminal proteases, bile salts and phospholipids played no role. Rate of release of an enzyme from the brush border bore no relationship to its rate of inactivation. When individual proteases were studied, elastase was the most potent for releasing disaccharidases from the brush border; trypsin was ineffective alone but augmented the effect of elastase. Sucrase and maltase were activated by proteolytic release, but activation was abolished by simultaneous exposure of brush borders to bile salts. Lactase was released and rapidly inactivated by proteinases, while alkaline phosphatase appeared to be inactivated without significant release. These results show that there are significant interactions between luminal factors which have been inapparent when studying them in isolation. Loss of functionally useful enzyme does not follow release of sucrase or maltase from the brush border into the lumen but does follow release of lactase. Study of the susceptibility of lactase to inactivation by luminal factors in the various forms of lactose intolerance is warranted. 相似文献
45.
46.
47.
The reactions of aliphatic and aromatic amines with reducing sugars are important in both drug stability and synthesis. The
formation of glycosylamines in solution, the first step in the Maillard reaction, does not typically cause browning but results
in decreased potency and is hence significant from the aspect of drug instability. The purpose of this research was to present
(1) unreported ionic equilibria of model reactant (kynurenine), (2) the analytical methods used to characterize and measure
reaction products, (3) the kinetic scheme used to measure reaction rates and (4) relevant properties of various reducing sugars
that impact the reaction rate in solution. The methods used to identify the reversible formation of two products from the
reaction of kynurenine and monosaccharides included LC mass spectrometry, UV spectroscopy, and 1-D and 2-D 1H–1H COSY NMR spectroscopy. Kinetics was studied using a stability-indicating HPLC method. The results indicated the formation
of α and β glycosylamines by a pseudo first-order reversible reaction scheme in the pH range of 1–6. The forward reaction
was a function of initial glucose concentration but not the reverse reaction. It was concluded that the reaction kinetics
and equilibrium concentrations of the glycosylamines were pH-dependent and also a function of the acyclic content of the reacting
glucose isomer. 相似文献
48.
49.
Electrical injury mechanisms: dynamics of the thermal response 总被引:1,自引:0,他引:1
The thermal response of the human upper extremity to large electric currents was examined using an axisymmetric unidimensional model containing bone, skeletal muscle, fat, and skin in coaxial cylindrical geometry. Appropriate thermal and electrical properties were assigned to each tissue, and the tissue response to joule heating was determined by a finite-element numerical technique. We found that when the tissues are electrically in parallel, skeletal muscle sustained the largest temperature rise and then heated adjacent tissues. Thus, when bone is not in series with other tissues, joule heating of bone is unlikely to be responsible for thermal damage to adjacent tissue. In addition, the effect of tissue perfusion on the thermal response was found to be essential for rapid cooling of the centrally located tissues. 相似文献
50.
J.-Y. Roh H.-W. Park Y.-H. Je D.-W. Lee B.-R. Jin H.-W. Oh S. S. Gill & S.-K. Kang 《Letters in applied microbiology》1997,24(6):451-454
Bacillus thuringiensis NTB-1 isolated from soil samples in Korea produces ovoidal parasporal inclusions with proteins of approximately 24–40 kDa in size. Although serological study indicated that the isolate has a flagella (H) antigen identical with subsp. israelensis , it seemed to be non-insecticidal against Lepidoptera and Coleoptera as well as Diptera. To investigate the activity of non-insecticidal B. thuringiensis transformed with insecticidal crystal protein genes, cryIVD and cytA genes of B. thuringiensis subsp. morrisoni PG-14, highly toxic to mosquito larvae, were introduced into the isolate NTB-1. The expression of mosquitocidal crystal protein genes in NTB-1 was characterized by SDS–PAGE analysis and electron microscopy. The results showed that crystalline inclusions of host, CryIVD and CytA were stably expressed in the transformant. However, the mosquitocidal activity of transformant was similar to that of B. thuringiensis subsp. kurstaki Cry− B harbouring cryIVD and cytA genes, demonstrating that a synergistic effect by an interaction of both introduced insecticidal and resident non-insecticidal crystal proteins was not observed. 相似文献