全文获取类型
收费全文 | 1771篇 |
免费 | 149篇 |
专业分类
1920篇 |
出版年
2024年 | 2篇 |
2023年 | 7篇 |
2022年 | 15篇 |
2021年 | 28篇 |
2020年 | 19篇 |
2019年 | 19篇 |
2018年 | 31篇 |
2017年 | 26篇 |
2016年 | 39篇 |
2015年 | 85篇 |
2014年 | 94篇 |
2013年 | 90篇 |
2012年 | 110篇 |
2011年 | 97篇 |
2010年 | 71篇 |
2009年 | 72篇 |
2008年 | 103篇 |
2007年 | 104篇 |
2006年 | 115篇 |
2005年 | 111篇 |
2004年 | 97篇 |
2003年 | 92篇 |
2002年 | 89篇 |
2001年 | 79篇 |
2000年 | 70篇 |
1999年 | 58篇 |
1998年 | 17篇 |
1997年 | 14篇 |
1996年 | 13篇 |
1995年 | 12篇 |
1994年 | 13篇 |
1993年 | 9篇 |
1992年 | 21篇 |
1991年 | 13篇 |
1990年 | 15篇 |
1989年 | 11篇 |
1988年 | 7篇 |
1987年 | 6篇 |
1986年 | 9篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1975年 | 3篇 |
1972年 | 4篇 |
1969年 | 4篇 |
1965年 | 1篇 |
1963年 | 1篇 |
排序方式: 共有1920条查询结果,搜索用时 11 毫秒
91.
On the origin of modular variation 总被引:10,自引:1,他引:9
Lipson H Pollack JB Suh NP 《Evolution; international journal of organic evolution》2002,56(8):1549-1556
We study the dynamics of modularization in a minimal substrate. A module is a functional unit relatively separable from its surrounding structure. Although it is known that modularity is useful both for robustness and for evolvability (Wagner 1996), there is no quantitative model describing how such modularity might originally emerge. Here we suggest, using simple computer simulations, that modularity arises spontaneously in evolutionary systems in response to variation, and that the amount of modular separation is logarithmically proportional to the rate of variation. Consequently, we predict that modular architectures would appear in correlation with high environmental change rates. Because this quantitative model does not require any special substrate to occur, it may also shed light on the origin of modular variation in nature. This observed relationship also indicates that modular design is a generic phenomenon that might be applicable to other fields, such as engineering: Engineering design methods based on evolutionary simulation would benefit from evolving to variable, rather than stationary, fitness criteria, as a weak and problem-independent method for inducing modularity. 相似文献
92.
Role of proto-oncogenes in the regulation of proenkephalin mRNA expression induced by repeated nicotine injections in rat adrenal medulla 总被引:2,自引:0,他引:2
We have studied the effect of repeated systemic administrations of nicotine (3 mg/kg) at 30 min intervals on proenkephalin (proENK) mRNA level in rat adrenal gland. Northern blot analysis has shown that proENK mRNA expression was enhanced by repeated nicotine administrations. Additionally, repeated administrations of nicotine transiently induced the c-fos and c-jun mRNA levels after the first-third nicotine administration, and the c-fos and c-jun mRNA levels were returned to the basal level after the seventh administration of nicotine. c-Fos, c-Jun and Fra-2 protein levels were persistently increased until the seventh administration. The repeated nicotine administrations also elevated phospho-CREB without altering total CREB level in all tested groups. Immunohistochemical analysis showed that the increase of c-Fos and c-Jun proteins by repeated nicotine administrations is mostly medulla specific, while Fra-2 immuno reactivity was shown both in medulla and cortex. The repeated nicotine administrations enhanced the AP-1 and ENKCRE-2 DNA binding activities. Furthermore, the cross-competition studies revealed that the AP-1 proteins, rather than CREB, actively bind to ENKCRE-2 DNA domain. These results suggest that proENK mRNA expression induced by repeated nicotine administrations may be mediated by AP-1 proteins, such as c-Fos, c-Jun and Fra-2 rather than CREB via interacting to the ENKCRE-2 DNA binding domain in rat adrenal medulla. 相似文献
93.
Green fluorescent protein-labeled recombinant fluobody for detecting the picloram herbicide 总被引:1,自引:0,他引:1
Kim IS Shim JH Suh YT Yau KY Hall JC Trevors JT Lee H 《Bioscience, biotechnology, and biochemistry》2002,66(5):1148-1151
A green fluorescent protein-labeled fluobody was designed to develop a simple immunoassay method for detecting picloram herbicide in an environmental sample. The gfp gene was successfully inserted into the pSJF2 vector harboring the picloram-specific antibody fragment to yield pSJF2GFP. Picloram spiking in an environmental river sample could be indirectly detected by observing the fluorescence intensity value of the gfp-fluobody, exhibiting specific sensitivity to free picloram with an IC50 value of 50 ppb. Using the gfp-fluobody immunoassay avoids the enzyme-substrate reaction for calorimetric detection that is required in an enzyme-linked immunosorbent assay (ELISA). 相似文献
94.
The 22 kDa Kunitz-type potato proteinase inhibitor (22 kDa KPPI) was induced in tubers. However, the 27 kDa protein, which is immunologically related to the 22 kDa KPPI, was induced in leaves by wounding, hormones, and environmental stresses. The leaf-specific 27 kDa protein was induced in leaves that were treated with exogenous abscisic acid (ABA), ethephon, methyl jasmonate (MeJA), and water deficit. These results indicate that the 27 kDa protein in leaves could function as a defense protein against mechanical damages by herbivorous animals and abiotic environmental stresses that could induce plant hormones. 相似文献
95.
The success of gene therapy is largely dependent on the delivery vector system. Efficient transfection and nontoxicity are two of the most important requirements of an ideal gene delivery vector. To generate both an efficient and nontoxic vector, we rationally constructed polymeric vectors to have simultaneous multiple functions, i.e., controlled degradation, an endosome disruptive function, and positive charges. Remarkably, the transfection efficiency of network poly(amino ester) (n-PAE) synthesized in this manner was comparable to that of polyethylenimine (PEI), one of the most efficient polymeric gene delivery vectors reported to date. However, there was a marked difference in cytotoxicity between the polymers. The majority of PEI-transfected cells were granulated and dead, whereas most of the cells transfected with n-PAE were viable and healthy. Successive events of efficient endosome escape of n-PAE/DNA polyplex and n-PAE biodegradation should result in high transfection efficiency and favorable cell viability response. The n-PAE-mediated transfection was also very efficient in the presence of serum. These data show that the approach we applied is a very appropriate way of making an ideal gene delivery carrier. 相似文献
96.
A novel colonic repressor element regulates intestinal gene expression by interacting with Cux/CDP
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Boudreau F Rings EH Swain GP Sinclair AM Suh ER Silberg DG Scheuermann RH Traber PG 《Molecular and cellular biology》2002,22(15):5467-5478
Intestinal gene regulation involves mechanisms that direct temporal expression along the vertical and horizontal axes of the alimentary tract. Sucrase-isomaltase (SI), the product of an enterocyte-specific gene, exhibits a complex pattern of expression. Generation of transgenic mice with a mutated SI transgene showed involvement of an overlapping CDP (CCAAT displacement protein)-GATA element in colonic repression of SI throughout postnatal intestinal development. We define this element as CRESIP (colon-repressive element of the SI promoter). Cux/CDP interacts with SI and represses SI promoter activity in a CRESIP-dependent manner. Cux/CDP homozygous mutant mice displayed increased expression of SI mRNA during early postnatal development. Our results demonstrate that an intestinal gene can be repressed in the distal gut and identify Cux/CDP as a regulator of this repression during development. 相似文献
97.
Chun J Kwon T Lee E Suh PG Choi EJ Sun Kang S 《Biochemical and biophysical research communications》2002,298(2):207-215
The Na(+)/H(+) exchanger regulatory factor 2 (NHERF2/TKA-1/E3KARP) contains two PSD-95/Dlg/ZO-1 (PDZ) domains which interact with the PDZ docking motif (X-(S/T)-X-(V/L)) of proteins to mediate the assembly of transmembrane and cytosolic proteins into functional signal transduction complexes. One of the PDZ domains of NHERF2 interacts specifically with the DSLL, DSFL, and DTRL motifs present at the carboxy-termini of the 2-adrenergic receptor, the platelet-derived growth factor receptor, and the cystic fibrosis transmembrane conductance regulator, respectively. Serum- and glucocorticoid-induced protein kinase 1 (SGK1) also carries a putative PDZ-binding motif (D-S-F-L) at its carboxy tail, implicated in the specific interaction with NHERF2. There is a 3-phosphoinositide-dependent protein kinase 1 (PDK1) interacting fragment (PIF) in the tail of NHERF2. Using pull-down assays and co-transfection experiments, we demonstrated that the DSFL tail of SGK1 interacts with the first PDZ domain of NHERF2 and the PIF of NHERF2 binds to the PIF-binding pocket of PDK1 to form an SGK1-NHERF2-PDK1 complex. Formation of the protein complex promoted the phosphorylation and activation of SGK1 by PDK1. Thus, it was suggested that NHERF2 mediates the activation and phosphorylation of SGK1 by PDK1 through its first PDZ domain and PIF motif, as a novel SGK1 activation mechanism. 相似文献
98.
Bae JH Mun KC Park WK Lee SR Suh SI Baek WK Yim MB Kwon TK Song DK 《Biochemical and biophysical research communications》2002,290(5):1506-1512
We have investigated the protective effect of (-)-epigallocatechin gallate (EGCG) on alpha-amino-3-hydroxy-5-methyl-4-isoxazolo propionate (AMPA)-induced toxicity in cultured rat hippocampal neurons. Treatment of 24 h AMPA (10 microM) reduced the neuronal viability in both survival neuron counting and MTT reduction assay compared with control, with increase in cellular concentrations of hydrogen peroxide and malondialdehyde. These responses to AMPA were significantly blocked by co-treatments with EGCG (10 microM), which effect was very similar to the protective ability of a known antioxidant catalase (2000 U/ml). AMPA (50 microM) elicited the increase in intracellular calcium concentration ([Ca(2+)]i) on which EGCG significantly attenuated both peak amplitude and sustained nature of that [Ca(2+)]i increase in a dose-dependent manner. These data suggest that EGCG has a neuroprotective effect against AMPA through inhibition of AMPA-induced [Ca(2+)]i increase and consequent attenuation of reactive oxygen species production and lipid peroxidation as an antioxidant and a radical scavenger. 相似文献
99.
Male-sterility of thermosensitive genic male-sterile rice is associated with premature programmed cell death of the tapetum 总被引:19,自引:0,他引:19
The tapetum plays a crucial role in pollen development. This secretory tissue produces numerous nutritive proteins necessary for pollen maturation. The tapetum, whose cells undergo programmed cell death (PCD), is completely diminished by the time the pollen is fully mature. Our previous studies on a thermosensitive genic male-sterile (TGMS) rice (Oryza sativa L.) suggested that male-sterility was due to failure in pollen development. In this paper we describe how further analysis of the TGMS rice revealed that male-sterility is associated with premature PCD of the tapetum. Cytological observations of TGMS rice anthers at various developmental stages indicated that PCD initiates at an early stage of pollen development and continues until the tapetal cells are completely degraded, resulting in pollen collapse. Transmission electron microscopy showed the morphologically distinct hallmarks of apoptosis, including cytoplasmic shrinkage, membrane blebbing, and vacuolation. Identification of DNA fragmentation using the TUNEL assay supports the hypothesis that premature PCD is associated with male-sterility in the rice. The tissue-specific feature of the thermosensitive genic male-sterile phenotype is discussed with regard to PCD during anther development. 相似文献
100.
Histone H2AX: a dosage-dependent suppressor of oncogenic translocations and tumors 总被引:23,自引:0,他引:23
Bassing CH Suh H Ferguson DO Chua KF Manis J Eckersdorff M Gleason M Bronson R Lee C Alt FW 《Cell》2003,114(3):359-370
We employed gene targeting to study H2AX, a histone variant phosphorylated in chromatin surrounding DNA double-strand breaks. Mice deficient for both H2AX and p53 (H(delta/delta)P(-/-)) rapidly developed immature T and B lymphomas and solid tumors. Moreover, H2AX haploinsufficiency caused genomic instability in normal cells and, on a p53-deficient background, early onset of various tumors including more mature B lymphomas. Most H2AX(delta/delta)p53(-/-) or H2AX(+/delta)p53(-/-) B lineage lymphomas harbored chromosome 12 (IgH)/15 (c-myc) translocations with hallmarks of either aberrant V(D)J or class switch recombination. In contrast, H2AX(delta/delta)p53(-/-) thymic lymphomas had clonal translocations that did not involve antigen receptor loci and which likely occurred during cellular expansion. Thus, H2AX helps prevent aberrant repair of both programmed and general DNA breakage and, thereby, functions as a dosage-dependent suppressor of genomic instability and tumors in mice. Notably, H2AX maps to a cytogenetic region frequently altered in human cancers, possibly implicating similar functions in man. 相似文献