全文获取类型
收费全文 | 1474篇 |
免费 | 188篇 |
国内免费 | 2篇 |
专业分类
1664篇 |
出版年
2023年 | 8篇 |
2022年 | 16篇 |
2021年 | 35篇 |
2020年 | 15篇 |
2019年 | 21篇 |
2018年 | 31篇 |
2017年 | 32篇 |
2016年 | 42篇 |
2015年 | 80篇 |
2014年 | 85篇 |
2013年 | 104篇 |
2012年 | 121篇 |
2011年 | 116篇 |
2010年 | 68篇 |
2009年 | 53篇 |
2008年 | 69篇 |
2007年 | 66篇 |
2006年 | 71篇 |
2005年 | 68篇 |
2004年 | 60篇 |
2003年 | 57篇 |
2002年 | 46篇 |
2001年 | 25篇 |
2000年 | 40篇 |
1999年 | 22篇 |
1998年 | 13篇 |
1997年 | 15篇 |
1996年 | 13篇 |
1995年 | 11篇 |
1994年 | 11篇 |
1993年 | 13篇 |
1992年 | 17篇 |
1991年 | 23篇 |
1990年 | 9篇 |
1989年 | 23篇 |
1988年 | 19篇 |
1987年 | 14篇 |
1986年 | 10篇 |
1985年 | 16篇 |
1984年 | 10篇 |
1983年 | 12篇 |
1982年 | 9篇 |
1981年 | 10篇 |
1980年 | 6篇 |
1979年 | 10篇 |
1978年 | 12篇 |
1976年 | 5篇 |
1973年 | 6篇 |
1971年 | 4篇 |
1968年 | 4篇 |
排序方式: 共有1664条查询结果,搜索用时 15 毫秒
61.
Cognitive schema were used to explain health and illness behaviors among Chinese students. University students in Hong Kong were asked to attribute causes and suggest solutions to five health/mental health problems: Weakness/Fatigue, Tension/ Anxiety, Sleep Difficulty, Hollow/Emptiness, and Headache. The patterns of endorsement on the causal and solution categories used for the five problems were compared using a new asymptotic chi-squared test. The response patterns were found to be significantly different across the five problems. Each problem was attributed to multiple causes including psychological, social, situational, somatic, and existential factors. The intended solutions were often related to the nature of the causal attributions especially when the problems were mild. In lay help-seeking, the Hong Kong students would attempt a variety of self-help measures. However, for professional consultation, the medical doctor would be the primary care professional the students would turn to for most of the problems except in the case of Hollow/Emptiness. 相似文献
62.
63.
B. Petersen C. J. Yee W. Bowen R. Zarnegar G. K. Michalopoulos 《Cell biology and toxicology》1994,10(4):219-230
TGF-1 is known as a potent inhibitor of proliferation of rat and human hepatocytes. In this study we show that the effects of TGF-1 are quite different on mouse hepatocytes. In rat and human hepatocytes, TGF-1 inhibited DNA synthesis and also inhibited the morphological changes induced by growth factors in rat and human hepatocytes. In contrast, addition of TGF-1 to mouse hepatocytes resulted in pronounced alterations in morphology of these cells. These changes were similar to those induced by HGF and EGF. The induction of structural changes by TGF-1 was noted only in mouse hepatocytes. Mouse hepatocytes were also much more resistant to the mito-inhibitory effect of TGF-1. These findings suggest profound differences in hepatocyte growth regulation between these species and may relate to observed differences in susceptibility to carcinogenesis.Abbreviations EGF
epidermal growth factor
- HGF
hepatocyte growth factor
- SF
scatter factor
- TGF-1
transforming growth factor beta type one 相似文献
64.
Yu-Ling Shih Ling-Ting Huang Yu-Ming Tu Bo-Fan Lee Yu-Chiuan Bau Chia Yee Hong Hsiao-lin Lee Yan-Ping Shih Min-Feng Hsu Zheng-Xin Lu Jui-Szu Chen Ling Chao 《Biophysical journal》2019,116(8):1469-1482
Heterogeneous distribution of components in the biological membrane is critical in the process of cell polarization. However, little is known about the mechanisms that can generate and maintain the heterogeneous distribution of the membrane components. Here, we report that the propagating wave patterns of the bacterial Min proteins can impose steric pressure on the membrane, resulting in transport and directional accumulation of the component in the membrane. Therefore, the membrane component waves represent transport of the component in the membrane that is caused by the steric pressure gradient induced by the differential levels of binding and dissociation of the Min proteins in the propagating waves on the membrane surface. The diffusivity, majorly influenced by the membrane anchor of the component, and the repulsed ability, majorly influenced by the steric property of the membrane component, determine the differential spatial distribution of the membrane component. Thus, transportation of the membrane component by the Min proteins follows a simple physical principle, which resembles a linear peristaltic pumping process, to selectively segregate and maintain heterogeneous distribution of materials in the membrane.
Video Abstract
65.
An alamethicin, secreted by the fungus Trichoderma viride and containing a glutamine at position 18 instead of the usual glutamic acid, has been uniformly labeled with 15N and purified by HPLC. The extent of 15N incorporation at individual backbone and side-chain sites was found to vary from 85% to 92%, as measured by spin-echo difference spectroscopy. The proton NMR spectrum of the peptide dissolved in methanol was assigned using correlation spectroscopies and nuclear Overhauser enhancements (NOE) measured in the rotating frame. The 15N resonances were assigned by the 2D 1H-15N correlation via heteronuclear multiple-quantum coherence experiment. NOEs and 3JNHC alpha H coupling constants strongly suggest that, in methanol, from Aib-3 to Gly-11, the peptide adopts a predominantly helical conformation, in agreement with previous 1H NMR studies [Esposito, G., Carver, J.A, Boyd, J., & Campbell, I.D. (1987) Biochemistry 26, 1043-1050; Banerjee, U., Tsui, F.-P., Balasubramanian, T.N., Marshall, G.R., & Chan, S I. (1983) J. Mol. Biol. 165, 757-775]. The conformation of the carboxyl terminus (12-20) is less well determined, partly because the amino acid composition reduces the number of NOEs and coupling constants which can be determined by 1H NMR spectroscopy. The 3JNHC alpha H in the C-terminus suggest the possibility of conformational averaging at Leu-12, Val-15, and Gln-19, an interpretation which is supported by a recent molecular dynamics simulation of the peptide [Fraternalli, F. (1990) Biopolymers 30, 1083-1099].(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
66.
Cort JR Yee A Edwards AM Arrowsmith CH Kennedy MA 《Journal of structural and functional genomics》2000,1(1):15-25
The solution structure of MTH1175, a 124-residue protein from the archaeon Methanobacterium thermoautotrophicum has been determined
by NMR spectroscopy. MTH1175 is part of a family of conserved hypothetical proteins (COG1433) with unknown functions which
contains multiple paralogs from all complete archaeal genomes and the archaeal gene-rich bacterium Thermotoga maritima. Sequence
similarity indicates this protein family may be related to the nitrogen fixation proteins NifB and NifX. MTH1175 adopts an
α/β topology with a single mixed β-sheet, and contains two flexible loops and an unstructured C-terminal tail. The fold resembles
that of Ribonuclease H and similar proteins, but differs from these in several respects, and is not likely to have a nuclease
activity.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
67.
68.
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor modulating a variety of biological functions including cancer cell proliferation and differentiation. However, the role of PPARgamma and its ligands in tumor invasion is unclear. To evaluate a possible role for PPARgamma ligands in tumor invasion, we examined whether PPARgamma agonists including pioglitazone, troglitazone, rosiglitazone, and ciglitazone could affect the activity of matrix metalloproteinases (MMPs) in the HT1080 cell line, a well-studied and well-characterized cell line for MMP research. The gelatin zymography assay showed that ciglitazone activated pro-MMP-2 significantly. In addition, ciglitazone increased the expression of MMP-2, which was accompanied by an increase of membrane type 1-MMP (MT1-MMP) expression. The PPARgamma antagonist, GW9662 attenuated the ciglitazone-induced PPARgamma activation but it did not affect the pro-MMP2 activation by ciglitazone, suggesting that the action of ciglitazone on the pro-MMP-2 activation bypassed the PPARgamma pathway. Antioxidants and various inhibitors of signal transduction were used to investigate the mechanism of ciglitazone-induced pro-MMP-2 activation. We found that the sustained production of reactive oxygen species (ROS) was required for pro-MMP-2 activation by ciglitazone. We also found that PB98059, an inhibitor of MEK-ERK, significantly blocked ciglitazone-induced pro-MMP-2 activation and that extracellular signal-regulated kinase (ERK) was hyperphosphorylated by ciglitazone. Moreover, cell invasion was significantly increased by ciglitazone in the HT1080 cell lines, whereas cell motility was not affected. This study suggests that ciglitazone-induced pro-MMP-2 activation increases PPARgamma-independent tumor cell invasion through ROS production and ERK activation in some types of cancer cells. 相似文献
69.
Investigations of competitive interactions emphasize non-detrital resources, even though detritus is a major component of most food webs. Studies of competing species focus usually on single resource types, although consumers in nature are likely to encounter mixtures of resource types that may affect whether competition results in exclusion or coexistence. The invasive mosquito Aedes albopictus is capable of excluding the native mosquito Ochlerotatus triseriatus in competition for single detritus types in laboratory and field microcosms. In this study, we used nine ratios of two detritus types (animal and leaf) common in natural containers to test whether detritus ratios affect the outcome of competition. Under intraspecific and interspecific competition, A. albopictus attained higher survival and estimated population growth rate than did O. triseriatus. Unlike past studies, both species had positive growth and high adult survival, with little evidence of competitive effects, under one resource ratio (10:1 ratio of leaf : animal detritus) regardless of mosquito densities, suggesting potential coexistence. Path analysis showed that densities of larvae had negative effects on population growth for O. triseriatus but not for A. albopictus, indicating competitive superiority of A. albopictus. Population growth of both species was affected strongly by the direct paths from animal (positive) and leaf (negative) detritus, and the indirect effect of leaf detritus via bacterial production (positive). Field sampling established that detritus entered real tree holes in ratios similar to those in our experiment, suggesting that natural variation in detritus ratios may influence local coexistence of these species. Seasonal variation in ratios of plant and animal detritus indicated that temporal as well as spatial variation in inputs may be important for potential coexistence. 相似文献
70.
The SARS-associated coronavirus (SARS-CoV) main proteinase is a key enzyme in viral polyprotein processing. To allow structure-based design of drugs directed at SARS-CoV main proteinase, we predicted its binding pockets and affinities with existing HIV, psychotic and parasite drugs (lopinavir, ritonavir, niclosamide and promazine), which show signs of inhibiting the replication of SARS-CoV. Our results suggest that these drugs and another two HIV inhibitors (PNU and UC2) could be used as templates for designing SARS-CoV proteinase inhibitors. 相似文献