全文获取类型
收费全文 | 537篇 |
免费 | 31篇 |
专业分类
568篇 |
出版年
2023年 | 2篇 |
2021年 | 3篇 |
2020年 | 5篇 |
2019年 | 8篇 |
2018年 | 5篇 |
2017年 | 6篇 |
2016年 | 12篇 |
2015年 | 23篇 |
2014年 | 20篇 |
2013年 | 27篇 |
2012年 | 39篇 |
2011年 | 47篇 |
2010年 | 19篇 |
2009年 | 21篇 |
2008年 | 39篇 |
2007年 | 38篇 |
2006年 | 23篇 |
2005年 | 19篇 |
2004年 | 24篇 |
2003年 | 27篇 |
2002年 | 31篇 |
2001年 | 2篇 |
2000年 | 5篇 |
1999年 | 7篇 |
1998年 | 13篇 |
1997年 | 6篇 |
1996年 | 9篇 |
1995年 | 6篇 |
1994年 | 4篇 |
1993年 | 7篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1989年 | 4篇 |
1988年 | 6篇 |
1987年 | 5篇 |
1985年 | 5篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1981年 | 6篇 |
1980年 | 10篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1966年 | 1篇 |
1960年 | 2篇 |
1927年 | 1篇 |
排序方式: 共有568条查询结果,搜索用时 0 毫秒
1.
2.
Proenkephalin encodes a group of small peptides with opiate-like activity, the endogenous opioids, known to function as neurohormones, neuromodulators, and neurotransmitters. Recently, we have demonstrated that in addition to its abundance in fetal brain tissue, proenkephalin is highly expressed in nondifferentiated mesodermal cells of developing fetuses. We identified the skeletal tissues, bone, and cartilage as major sites of proenkephalin expression. To examine the possibility that proenkephalin is involved in bone development we have studied the expression of this gene in bone-derived cells, its modulation by bone active hormones, and the effects of enkephalin-derived peptides on osteoblastic phenotype. Our studies revealed that osteoblastic cells synthesize high levels of proenkephalin mRNA which are translated, and the derived peptides are secreted. Reciprocal interrelationships between osteoblast maturation and proenkephalin expression were established. These results together with our observations demonstrating inhibitory effects of proenkephalin-derived peptides on osteoblastic alkaline phosphatase activity, strongly support the notion that proenkephalin is involved in bone development. A different direction of research by other investigators has established the capability of the opioid system in the periphery to participate in the control of pain. On the basis of these two lines of observation, we would like to present the following hypothesis: The potential of embryonic skeletal tissue to synthesize proenkephalin-derived peptides is retained in the adult in small defined undifferentiated cell populations. This potential is realized in certain situations requiring rapid growth, such as remodeling or fracture repair. We suggest that in these processes, similarly to the situation in the embryo, the undifferentiated dividing cells produce the endogenous opioids. In the adult these peptides may have a dual function, namely participating in the control of tissue regeneration and in the control of pain. © 1994 Wiley-Liss, Inc. 相似文献
3.
Vered Barenholz-Paniry Jacob S. Ishay Zvi Grossman 《Bulletin of mathematical biology》1988,50(6):661-679
Rhythmic “circa-second” contrations of larvae of the hornetVespa orientalis, believed to serve as hunger signals, were studied. A considerable degree of coordination among individual larvae, both in
frequency and phase of these contractions, has been observed. The oscillations of singly isolated larvae are of short duration,
non-constant, with increasing intervals in between and there is a substantial variability in the patterns shown by different
larvae. In contrast, the association of two or more larvae leads to enhancement of their periodic behaviour and to (partial)
entrainment. Communication among larvae may perhaps be mediated by the sound pulses (“scratching” noises) which are generated
by these contractions. We have subjected individual and grouped larvae to external sound pulses and were able to demonstrate:
(a) enhancement of rhythmic activity; (b) phase resetting; (c) entrainment to an external oscillator within a range of frequencies;
(d) the existence of a subharmonic mode of entrainment. We propose a simple phenomenologic model to account for these larvae
responses. Our model assumes the existence of an “energy” variable which declines with time but is upgraded, in a phase-dependent
way, by external stimuli.
Based in part on work performed by V. Barenholz-Paniry in partial fulfillment of the requirements for the M.Sc. degree from
the Sackler Faculty of Medicine, Tel Aviv University, 1986. 相似文献
4.
The mechanism ofStaphylococcus aureus inactivation by deuteroporphyrin (DT) and light was studied with singlet oxygen quenchers or hydroxyl radical scavengers. The light-activated DT (10 /ml) reduced the viability of the culture to less than 1%, whereas methionine, tryptophan, and 1,4-diazabicyclo-2,2,2-octane (DBCO) used as singlet oxygen quenchers provided almost 60% protection. Propylgallate, which is a hydroxyl free radical scavenger, also provided 60% protection. The presence of a singlet oxygen quencher and propylgallate provided almost complete protection from inactivation (96%). Photoinactivation in the absence of culture media (in saline) increased the killing rate and decreased the ability of the singlet oxygen quenchers to protect. In the same conditions damage from hydroxl free radicals was well protected by propyl gallate. The present results indicate thatS. aureus photoinactivation by DT and light is mediated by both singlet oxygen and hydroxyl free radicals. 相似文献
5.
Hagit Shapira Meir Mouallem Menachem S. Shapiro Yosef Weisman Zvi Farfel 《Human genetics》1996,97(1):73-75
Pseudohypoparathyroidism type Ia (PHP-Ia) is a hereditary disease characterized by resistance to PTH and other hormones that act via cAMP. Patients have deficient activity of Gs, the subunit of the G protein, which couples hormone receptors to stimulation of adenylate cyclase. We describe two new mutations discovered in two sporadic patients with PHP-Ia. Using genomic DNA, we have amplified exons 2–13 of the Gs gene (GNAS1) by PCR, and sequenced the resulting products. Both patients had Albright's hereditary osteodystrophy, resistance to multiple hormones, and deficient Gs activity. In the first patient, a deletion of a C in exon 5 at codon 115 was found. In the second patient, an insertion of a C in exon 10 at codon 267 was detected. Both these heterozygous mutations cause frameshift, and predict decreased production of Gs. This report adds two new Gs mutations to the known ten mutations recently described. 相似文献
6.
Avraham Geier Rachel Beery Michal Haimsohn Rina Hemi Zvi Malik Avraham Karasik 《In vitro cellular & developmental biology. Animal》1994,30(12):867-874
Summary The ability of epidermal growth factor (EGF), insulinlike growth factor-1 (IGF-1), insulin, 12-O-tetradecanoylphorbol-13-acetate
(TPA), and aurintricarboxylic acid (ATA) to protect the human breast cancer cell line MDA-231 from death induced by the anticancer
drug adriamycin was investigated. Cell death was induced in the MDA-231 cells either by a short-time exposure to a high dose
of adriamycin (2 μg · ml−1 · 1 h−1) and further culturing in the absence of the drug, or by continuous exposure to a low dose of adriamycin (0.3μg/ml). Cell death was evaluated after 48 h of incubation by several techniques (trypan blue dye exclusion, lactic dehydrogenase
activity, cellular ATP content, transmission electron microscopy, and DNA fragmentation). EGF, TPA, and ATA, each at an optimal
concentration of 20 ng/ml, 5 ng/ml, and 100μg/ml respectively, substantially enhanced survival of cells exposed either to a high or low dose of adriamycin. Neither IGF-1
nor insulin, each at concentrations of 20 ng/ml, had an effect on cell survival. The three survival factors enhanced protein
synthesis in the untreated cells and attenuated the continuous decrease in protein synthesis in the adriamycin-treated cells.
Moreover, the three survival factors protected the MDA-231 cells from death in the absence of protein synthesis (cycloheximide
30μg/ml). These results suggest that EGF, TPA, and ATA promote survival of adriamycin pretreated cells by at least two mechanisms:
enhancement of protein synthesis and by a protein synthesis independent process, probably a posttranslational modification
effect. 相似文献
7.
Parietochloris incisa comb. nov. (Trebouxiophyceae, Chlorophyta) 总被引:3,自引:0,他引:3
Shin Watanabe Seishiro Hirabayashi Sammy Boussiba Zvi Cohen Avigad Vonshak Amos Richmond 《Phycological Research》1996,44(2):107-108
A coccoid green alga, Myrmecia incisa Reisigl, was isolated from the soil of Mt Tateyama, Japan. Electronmicroscopy revealed that the organism has pyrenoids sparsely covered with starch segments and traversed by many parallel thylakoid membranes, and zoo-spores with counterclockwise basal body orientation. Due to the presence of these features, we have proposed a reclassification of M. incisa into the genus Parietochloris, Trebouxiophyceae. 相似文献
8.
Shlomit Katz Zvy Dubinsky Chana Rothmann Zvi Malik Michael Friedlander 《Journal of phycology》1997,33(3):425-432
The novel method of Fourier transform multi-pixel spectroscopy was used for the nondestructive analysis of and comparison of pigmentation in different regions of live thalli of the red alga Porphyra linearis. Because the thallus in this alga consists of a monolayer of nonoverlapping cells, we were able to analyze the pigmentation of single cells by combining light absorbance with natural fluorescence data. From the image of each cell in the vegetative male and female reproductive and holdfast regions, more than 4 ± 104 fluorescence and absorbance spectra were obtained. Specific pigments in the different regions were localized by the use of a software program of similarity mapping followed by image construction. The reconstructed images revealed subcellular localization of each pigment according to specific spectroscopic fingerprints. The results showed that the vegetative and female reproductive cell types had a significantly higher content of phycoerythrin than of phycocyanin, and quite similar chlorophyll a levels. Most of the holdfast cells were poorly pigmented, but had more chlorophyll a than phycoerythrin or phycocyanin. The male reproductive cells contained only traces of pigments. Thus, by using Fourier transform multipixel spectroscopy, we were able to characterize the pigmentation of different regions of the thallus and follow the distribution patterns of the different pigments on the subcellular level along the differentiation gradient of the alga. 相似文献
9.
Anat Zvi Naomi Ariel John Fulkerson Jerald C Sadoff Avigdor Shafferman 《BMC medical genomics》2008,1(1):1-25
Background
Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), infects ~8 million annually culminating in ~2 million deaths. Moreover, about one third of the population is latently infected, 10% of which develop disease during lifetime. Current approved prophylactic TB vaccines (BCG and derivatives thereof) are of variable efficiency in adult protection against pulmonary TB (0%–80%), and directed essentially against early phase infection.Methods
A genome-scale dataset was constructed by analyzing published data of: (1) global gene expression studies under conditions which simulate intra-macrophage stress, dormancy, persistence and/or reactivation; (2) cellular and humoral immunity, and vaccine potential. This information was compiled along with revised annotation/bioinformatic characterization of selected gene products and in silico mapping of T-cell epitopes. Protocols for scoring, ranking and prioritization of the antigens were developed and applied.Results
Cross-matching of literature and in silico-derived data, in conjunction with the prioritization scheme and biological rationale, allowed for selection of 189 putative vaccine candidates from the entire genome. Within the 189 set, the relative distribution of antigens in 3 functional categories differs significantly from their distribution in the whole genome, with reduction in the Conserved hypothetical category (due to improved annotation) and enrichment in Lipid and in Virulence categories. Other prominent representatives in the 189 set are the PE/PPE proteins; iron sequestration, nitroreductases and proteases, all within the Intermediary metabolism and respiration category; ESX secretion systems, resuscitation promoting factors and lipoproteins, all within the Cell wall category. Application of a ranking scheme based on qualitative and quantitative scores, resulted in a list of 45 best-scoring antigens, of which: 74% belong to the dormancy/reactivation/resuscitation classes; 30% belong to the Cell wall category; 13% are classical vaccine candidates; 9% are categorized Conserved hypotheticals, all potentially very potent T-cell antigens.Conclusion
The comprehensive literature and in silico-based analyses allowed for the selection of a repertoire of 189 vaccine candidates, out of the whole-genome 3989 ORF products. This repertoire, which was ranked to generate a list of 45 top-hits antigens, is a platform for selection of genes covering all stages of M. tuberculosis infection, to be incorporated in rBCG or subunit-based vaccines. 相似文献10.
Tom Bongiorno Jacob Kazlow Roman Mezencev Sarah Griffiths Rene Olivares-Navarrete John F. McDonald Zvi Schwartz Barbara D. Boyan Todd C. McDevitt Todd Sulchek 《Journal of biomechanics》2014
Although it has been established that cellular stiffness can change as a stem cell differentiates, the precise relationship between cell mechanics and other phenotypic properties remains unclear. Inherent cell heterogeneity and asynchronous differentiation complicate population analysis; therefore, single-cell analysis was employed to determine how changes in cell stiffness correlate with changes in molecular biomarkers during differentiation. Design of a custom gridded tissue culture dish facilitated single-cell comparisons between cell mechanics and other differentiation biomarkers by enabling sequential measurement of cell mechanics and protein biomarker expression at the single cell level. The Young’s modulus of mesenchymal stem cells was shown not only to decrease during chemically-induced osteoblast differentiation, but also to correlate more closely with the day of differentiation than did the relative expression of the traditional osteoblast differentiation markers, bone sialoprotein and osteocalcin. Therefore, cell stiffness, a measurable property of individual cells, may serve as an improved indicator of single-cell osteoblast differentiation compared to traditional biological markers. Revelation of additional osteoblast differentiation indicators, such as cell stiffness, can improve identification and collection of starting cell populations, with applications to mesenchymal stem cell therapies and stem cell-based tissue engineering. 相似文献