全文获取类型
收费全文 | 250649篇 |
免费 | 13235篇 |
国内免费 | 13055篇 |
出版年
2024年 | 225篇 |
2023年 | 1820篇 |
2022年 | 4257篇 |
2021年 | 7998篇 |
2020年 | 5406篇 |
2019年 | 6779篇 |
2018年 | 16672篇 |
2017年 | 14102篇 |
2016年 | 13372篇 |
2015年 | 10526篇 |
2014年 | 12057篇 |
2013年 | 12983篇 |
2012年 | 18833篇 |
2011年 | 25198篇 |
2010年 | 19380篇 |
2009年 | 15159篇 |
2008年 | 17830篇 |
2007年 | 18570篇 |
2006年 | 7157篇 |
2005年 | 6120篇 |
2004年 | 5713篇 |
2003年 | 5265篇 |
2002年 | 4431篇 |
2001年 | 3387篇 |
2000年 | 3100篇 |
1999年 | 2822篇 |
1998年 | 1697篇 |
1997年 | 1676篇 |
1996年 | 1613篇 |
1995年 | 1417篇 |
1994年 | 1327篇 |
1993年 | 1016篇 |
1992年 | 1411篇 |
1991年 | 1115篇 |
1990年 | 892篇 |
1989年 | 755篇 |
1988年 | 635篇 |
1987年 | 601篇 |
1986年 | 426篇 |
1985年 | 476篇 |
1984年 | 279篇 |
1983年 | 293篇 |
1982年 | 184篇 |
1981年 | 149篇 |
1980年 | 102篇 |
1979年 | 153篇 |
1974年 | 94篇 |
1973年 | 99篇 |
1972年 | 329篇 |
1971年 | 317篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
181.
We used a N-biotinylated peptide analog of the C-terminal domain of the tumor suppressor protein, p21cip1/waf1 to elucidate peptide/protein interacting partners. The C-terminal domain of p21cip1/waf1 protein spanning 141-160 amino acid residues is known to bind PCNA and this interaction is important in many biological processes including cell-cycle control. This C-terminal 20-mer efficiently extracts PCNA in the presence of a variety of N- or C-terminally attached affinity tags. Using difference silver stained 2D gels combined with in-gel tryptic digests, we identified the difference spots using MALDI-TOF mass spectrometry-based peptide mass fingerprinting followed by a database search using PROFOUND against NCBIs human nonredundant protein sequence data bank. Identified spots include the p48 subunit of chromatin assembly factor-1, the heat shock 70 protein analog BiP, calmodulin, nucleolin and a spot similar in size to dimeric PCNA. In contrast, microcapillary ion-trap LC-MS/MS analysis of a tryptic digest of entire affinity extracts derived from both control and experimental runs followed by database searches using SEQUEST confirmed the presence of most of the above proteins. This strategy also identified hnRNPA1, HPSP90alpha, HSP40 and T-complex protein 1, a protein similar to prothymosin, and a possible allelic variant of the p21cip1/waf1 protein. The use of N-biotinylated peptide derived from the C-terminal domain of p21cip1/waf1 protein in proteomic analysis exemplified here suggests that peptides obtained from intracellular functional screens could also potentially serve as efficient baits to discover new drug targets. 相似文献
182.
A cDNA library was prepared from poly(A) mRNA extracted from 9-day hamster-yolk-sac erythroid cells. Two clones containing inserts coding for embryonic beta-like z or y globin-chains were isolated. Their identity was confirmed by (a) translation of hybrid selected mRNAs and (b) nucleotide sequence analysis of the inserts and comparison to the embryonic beta-like globin genes of Balb/c mouse. Availability of sequences for embryonic and adult globin cDNAs will aid in investigations of the molecular mechanisms of the globin switch in hamster YSEC. 相似文献
183.
184.
The number of orientation, feeding and social calls emitted by pipistrelle batsPipistrellus pipistrellus Schreber, 1774 andP. pygmaeus Leach, 1825 was recorded throughout the night at eight different sites. Social calls were unaffected by weather variables,
whereas orientation calls and feeding buzzes were both significantly affected by cloud and temperature conditions. The number
of emissions of each call type was significantly different between sites, indicating that the bats used different sites for
different activities. Significant positive correlations between all three combinations of call types occurred only during
the middle of the night, corresponding with the nadir of flying insects. This suggests that bats were engaged in activities
other than feeding at this time, such as territory protection or mate attraction. 相似文献
185.
186.
Background
NOL7 is a candidate tumor suppressor that localizes to a chromosomal region 6p23. This locus is frequently lost in a number of malignancies, and consistent loss of NOL7 through loss of heterozygosity and decreased mRNA and protein expression has been observed in tumors and cell lines. Reintroduction of NOL7 into cells resulted in significant suppression of in vivo tumor growth and modulation of the angiogenic phenotype. Further, NOL7 was observed to localize to the nucleus and nucleolus of cells. However, the mechanisms regulating its subcellular localization have not been elucidated. 相似文献187.
Alexander V. Kirdyanov Eugene A. Vaganov Malcolm K. Hughes 《Trees - Structure and Function》2007,21(1):37-44
We propose a technique for separating the climatic signal which is contained in two tree-ring parameters widely used in dendroclimatology.
The method is based on the removal of the relationship between tree-ring width (TRW) and maximum latewood density (MXD) observed
for narrow tree rings from high latitudes. The new technique is tested on data from three larch stands located along the northern
timberline in Eurasia. Correlations were calculated between the temperatures of pentads (five consecutive days), TRW chronologies
and MXD chronologies calculated according to the standard and proposed methods. The analysis confirms the great importance
of summer temperature for tree radial growth and tree-ring formation. TRW is positively correlated with the temperature of
four to eight pentads (depending on the region) at the beginning of the growth season, but MXD as obtained by the standard
technique is correlated with temperature over a much longer period. For maximum density series from which the relationship
between MXD and TRW has been removed (MXD′), there is a clear correlation with temperatures in the second part of the growing
season. These results are consistent with the known dynamics of tree-ring growth in high latitudes and mechanisms of tree-ring
formation. 相似文献
188.
Ovarian cancer G protein-coupled receptor 1 (OGR1) is a proton-sensing molecule that can detect decreases in extracellular pH that occur during inflammation. Although OGR1 has been shown to have pro-inflammatory functions in various diseases, its role in autoimmunity has not been examined. We therefore sought to determine whether OGR1 has a role in the development of T cell autoimmunity by contrasting the development of experimental autoimmune encephalomyelitis between wild type and OGR1-knockout mice. OGR1-knockout mice showed a drastically attenuated clinical course of disease that was associated with a profound reduction in the expansion of myelin oligodendrocyte glycoprotein 35-55-reactive T helper 1 (Th1) and Th17 cells in the periphery and a reduced accumulation of Th1 and Th17 effectors in the central nervous system. We determined that these impaired T cell responses in OGR1-knockout mice associated with a reduced frequency and number of dendritic cells in draining lymph nodes during EAE and a higher production of nitric oxide by macrophages. Our studies suggest that OGR1 plays a key role in regulating T cell responses during autoimmunity. 相似文献
189.
Zhenzhen Zhang Changjiu He Yu Gao Lu Zhang Yukun Song Tianqi Zhu Kuanfeng Zhu Dongying Lv Jing Wang Xiuzhi Tian Teng Ma Pengyun Ji Wei Cui Guoshi Liu 《Aging cell》2021,20(2)
The fecundity reduction with aging is referred as the reproductive aging which comes earlier than that of chronological aging. Since humans have postponed their childbearing age, to prolong the reproductive age becomes urgent agenda for reproductive biologists. In the current study, we examined the potential associations of α‐ketoglutarate (α‐KG) and reproductive aging in mammals including mice, swine, and humans. There is a clear tendency of reduced α‐KG level with aging in the follicle fluids of human. To explore the mechanisms, mice were selected as the convenient animal model. It is observed that a long term of α‐KG administration preserves the ovarian function, the quality and quantity of oocytes as well as the telomere maintaining system in mice. α‐KG suppresses ATP synthase and alterations of the energy metabolism trigger the nutritional sensors to down‐regulate mTOR pathway. These events not only benefit the general aging process but also maintain ovarian function and delay the reproductive decline. Considering the safety of the α‐KG as a naturally occurring molecule in energy metabolism, its utility in reproduction of large mammals including humans deserves further investigation. 相似文献
190.
Catalysis of ADP-ATP exchange by nucleotide exchange factors (NEFs) is central to the activity of Hsp70 molecular chaperones. Yet, the mechanism of interaction of this family of chaperones with NEFs is not well understood in the context of the sequence evolution and structural dynamics of Hsp70 ATPase domains. We studied the interactions of Hsp70 ATPase domains with four different NEFs on the basis of the evolutionary trace and co-evolution of the ATPase domain sequence, combined with elastic network modeling of the collective dynamics of the complexes. Our study reveals a subtle balance between the intrinsic (to the ATPase domain) and specific (to interactions with NEFs) mechanisms shared by the four complexes. Two classes of key residues are distinguished in the Hsp70 ATPase domain: (i) highly conserved residues, involved in nucleotide binding, which mediate, via a global hinge-bending, the ATPase domain opening irrespective of NEF binding, and (ii) not-conserved but co-evolved and highly mobile residues, engaged in specific interactions with NEFs (e.g., N57, R258, R262, E283, D285). The observed interplay between these respective intrinsic (pre-existing, structure-encoded) and specific (co-evolved, sequence-dependent) interactions provides us with insights into the allosteric dynamics and functional evolution of the modular Hsp70 ATPase domain. 相似文献