全文获取类型
收费全文 | 3301篇 |
免费 | 261篇 |
国内免费 | 2篇 |
专业分类
3564篇 |
出版年
2024年 | 3篇 |
2023年 | 18篇 |
2022年 | 40篇 |
2021年 | 61篇 |
2020年 | 38篇 |
2019年 | 41篇 |
2018年 | 51篇 |
2017年 | 48篇 |
2016年 | 88篇 |
2015年 | 145篇 |
2014年 | 163篇 |
2013年 | 218篇 |
2012年 | 251篇 |
2011年 | 263篇 |
2010年 | 181篇 |
2009年 | 177篇 |
2008年 | 241篇 |
2007年 | 232篇 |
2006年 | 200篇 |
2005年 | 199篇 |
2004年 | 203篇 |
2003年 | 165篇 |
2002年 | 177篇 |
2001年 | 53篇 |
2000年 | 31篇 |
1999年 | 32篇 |
1998年 | 35篇 |
1997年 | 26篇 |
1996年 | 18篇 |
1995年 | 23篇 |
1994年 | 11篇 |
1993年 | 14篇 |
1992年 | 7篇 |
1991年 | 10篇 |
1990年 | 9篇 |
1989年 | 6篇 |
1988年 | 9篇 |
1987年 | 4篇 |
1986年 | 5篇 |
1985年 | 9篇 |
1984年 | 5篇 |
1983年 | 11篇 |
1982年 | 12篇 |
1981年 | 8篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1978年 | 5篇 |
1977年 | 5篇 |
1976年 | 4篇 |
1973年 | 2篇 |
排序方式: 共有3564条查询结果,搜索用时 0 毫秒
91.
Seals may delay costly physiological processes (e.g. digestion) that are incompatible with the physiological adjustments to diving until after periods of active foraging. We present unusual profiles of metabolic rate (MR) in grey seals measured during long-term simulation of foraging trips (4-5 days) that provide evidence for this. We measured extremely high MRs (up to almost seven times the baseline levels) and high heart rates during extended surface intervals, where the seals were motionless at the surface. These occurred most often during the night and occurred frequently many hours after the end of feeding bouts. The duration and amount of oxygen consumed above baseline levels during these events was correlated with the amount of food eaten, confirming that these metabolic peaks were related to the processing of food eaten during foraging periods earlier in the day. We suggest that these periods of high MR represent a payback of costs deferred during foraging. 相似文献
92.
Systematic identification of SH3 domain-mediated human protein-protein interactions by peptide array target screening 总被引:1,自引:0,他引:1
Systematic identification of direct protein-protein interactions is often hampered by difficulties in expressing and purifying the corresponding full-length proteins. By taking advantage of the modular nature of many regulatory proteins, we attempted to simplify protein-protein interactions to the corresponding domain-ligand recognition and employed peptide arrays to identify such binding events. A group of 12 Src homology (SH) 3 domains from eight human proteins (Swiss-Prot ID: SRC, PLCG1, P85A, NCK1, GRB2, FYN, CRK) were used to screen a peptide target array composed of 1536 potential ligands, which led to the identification of 921 binary interactions between these proteins and 284 targets. To assess the efficiency of the peptide array target screening (PATS) method in identifying authentic protein-protein interactions, we examined a set of interactions mediated by the PLCgamma1 SH3 domain by coimmunoprecipitation and/or affinity pull-downs using full-length proteins and achieved a 75% success rate. Furthermore, we characterized a novel interaction between PLCgamma1 and hematopoietic progenitor kinase 1 (HPK1) identified by PATS and demonstrated that the PLCgamma1 SH3 domain negatively regulated HPK1 kinase activity. Compared to protein interactions listed in the online predicted human interaction protein database (OPHID), the majority of interactions identified by PATS are novel, suggesting that, when extended to the large number of peptide interaction domains encoded by the human genome, PATS should aid in the mapping of the human interactome. 相似文献
93.
Betel D Breitkreuz KE Isserlin R Dewar-Darch D Tyers M Hogue CW 《PLoS computational biology》2007,3(9):1783-1789
The multitude of functions performed in the cell are largely controlled by a set of carefully orchestrated protein interactions often facilitated by specific binding of conserved domains in the interacting proteins. Interacting domains commonly exhibit distinct binding specificity to short and conserved recognition peptides called binding profiles. Although many conserved domains are known in nature, only a few have well-characterized binding profiles. Here, we describe a novel predictive method known as domain–motif interactions from structural topology (D-MIST) for elucidating the binding profiles of interacting domains. A set of domains and their corresponding binding profiles were derived from extant protein structures and protein interaction data and then used to predict novel protein interactions in yeast. A number of the predicted interactions were verified experimentally, including new interactions of the mitotic exit network, RNA polymerases, nucleotide metabolism enzymes, and the chaperone complex. These results demonstrate that new protein interactions can be predicted exclusively from sequence information. 相似文献
94.
95.
Amy Forbes Mike Pickell Mehry Foroughian Li-Juan Yao James Lewis Ruud Veldhuizen 《Journal of applied physiology》2007,103(2):637-645
Pulmonary surfactant is a lipid-protein material that is essential for normal lung function. Maintaining normal and consistent alveolar amounts of surfactant is in part dependent on clearance of surfactant by alveolar macrophages (AM). The present study utilized a rat model of AM depletion to determine the impact on surfactant pool sizes and function over time. Male Sprague-Dawley rats were anesthetized and intratracheally instilled with PBS-liposomes (PBS-L) or dichloromethylene diphosphonic acid (DMDP) containing liposomes (DMDP-L) and were killed at various time points up to 21 days for compliance measurements, AM cell counts, and surfactant analysis. AM numbers were significantly decreased 1, 2, and 3 days after instillation in DMDP-L vs. PBS-L, with 72% depletion at 3 days. AM numbers returned to normal levels by 5 days. In DMDP-L rats, there was a rapid increase in surfactant-phospholipid pools, showing a ninefold increase in the amount of surfactant in the lavage 3 days after liposome instillation. Surfactant accumulation progressed up to 7 days, with pools normalizing by 21 days. The increase in surfactant was due to increases in both subfractions of surfactant, the large aggregates (LA) and small aggregates. Surfactant protein A levels, relative to LA phospholipids, were not increased. There was a decreased extent of surfactant conversion in vitro for LA from DMDP-L rats compared with controls. It is concluded that the procedure of AM depletion significantly affects surfactant metabolism. The increased endogenous surfactant must be considered when utilizing the AM depletion model to study the role of these cells during lung insults. 相似文献
96.
97.
Interaction of sauger Sander canadensis and walleye Sander vitreus in a large,shallow northern river
The objectives of this study were to: (1) determine the relative abundance of sauger Sander canadensis and walleye S. vitreus within the Rainy River using a standardized index netting technique; (2) assess the life-history characteristics of the two species in a northern river; (3) examine the spatial distribution of the two species; (4) assess year-class synchrony. At a larger scale, relative abundance of S. canadensis and S. vitreus were similar among sections of the river. However, at a finer scale, S. canadensis were the dominant species over more area (24%) of the river than S. vitreus (12%). Life-history traits for both species were within the range reported for North American. Mortality rates were similar, suggesting that anglers were not affecting one species more than the other. Year-class strengths were not synchronous between S. canadensis and S. vitreus (r = 0.07). There was evidence of S. canadensis potentially outcompeting S. vitreus with a strong year class of S. canadensis followed by a very weak class of S. vitreus. Additionally, S. canadensis were larger than S. vitreus in most sections of the river when adjusted for mean size. However, the potential interspecific competition was not to the exclusion of S. vitreus. Turbidity was probably the factor that enable S. canadensis to survive sympatrically with S. vitreus given their inability to segregate by depth within the river. 相似文献
98.
Gregor Schlüter Arzu Celik Renato Obata Mike Schlicker Sigrun Hofferbert Astrid Schlung Ibrahim M. Adham Wolfgang Engel 《Molecular reproduction and development》1996,43(1):1-6
Structural data are presented on the protamine gene cluster (PGC) of human, mouse, rat, and bull. By restriction mapping we demonstrate that the organization of the protamine cluster is conserved throughout all four species, i.e., the genes are situated in a head to tail arrangement in the order: protamine l-protamine 2-transition protein 2. Further, we established the nucleotide sequence of the entire human PGC (25 kb in total) and the 3′ portion of the rat protamine cluster (PRM2 and TNP2 genes and intergenic region). In addition, a 1 kb fragment of the bovine and murine protamine cluster, situated between PRM2 and TNP2, was sequenced. This fragment is conserved regarding sequence, position, and orientation in all species examined, and was classified as likely coding region by gene recognition program GRAIL. Using the rat fragment as a probe in RNA blots, we detected a testis-specific signal of about 0.5 kb. Finally, we demonstrate a high density of Alu elements, both full and fragmented copies, in the human PGC and discuss their localization with respect to evolutionary and functional aspects. © 1996 Wiley-Liss, Inc. 相似文献
99.
Dimitra Sakoula Garrett J. Smith Jeroen Frank Rob J. Mesman Linnea F. M. Kop Pieter Blom Mike S. M. Jetten Maartje A. H. J. van Kessel Sebastian Lücker 《The ISME journal》2022,16(4):958
The advance of metagenomics in combination with intricate cultivation approaches has facilitated the discovery of novel ammonia-, methane-, and other short-chain alkane-oxidizing microorganisms, indicating that our understanding of the microbial biodiversity within the biogeochemical nitrogen and carbon cycles still is incomplete. The in situ detection and phylogenetic identification of novel ammonia- and alkane-oxidizing bacteria remain challenging due to their naturally low abundances and difficulties in obtaining new isolates from complex samples. Here, we describe an activity-based protein profiling protocol allowing cultivation-independent unveiling of ammonia- and alkane-oxidizing bacteria. In this protocol, 1,7-octadiyne is used as a bifunctional enzyme probe that, in combination with a highly specific alkyne-azide cycloaddition reaction, enables the fluorescent or biotin labeling of cells harboring active ammonia and alkane monooxygenases. Biotinylation of these enzymes in combination with immunogold labeling revealed the subcellular localization of the tagged proteins, which corroborated expected enzyme targets in model strains. In addition, fluorescent labeling of cells harboring active ammonia or alkane monooxygenases provided a direct link of these functional lifestyles to phylogenetic identification when combined with fluorescence in situ hybridization. Furthermore, we show that this activity-based labeling protocol can be successfully coupled with fluorescence-activated cell sorting for the enrichment of nitrifiers and alkane-oxidizing bacteria from complex environmental samples, enabling the recovery of high-quality metagenome-assembled genomes. In conclusion, this study demonstrates a novel, functional tagging technique for the reliable detection, identification, and enrichment of ammonia- and alkane-oxidizing bacteria present in complex microbial communities.Subject terms: Environmental microbiology, Sequencing, Microbiology 相似文献
100.
Takada A Feldmann H Stroeher U Bray M Watanabe S Ito H McGregor M Kawaoka Y 《Journal of virology》2003,77(2):1069-1074
Ebola virus causes lethal hemorrhagic fever in humans, but currently there are no effective vaccines or antiviral compounds for this infectious disease. Passive transfer of monoclonal antibodies (MAbs) protects mice from lethal Ebola virus infection (J. A. Wilson, M. Hevey, R. Bakken, S. Guest, M. Bray, A. L. Schmaljohn, and M. K. Hart, Science 287:1664-1666, 2000). However, the epitopes responsible for neutralization have been only partially characterized because some of the MAbs do not recognize the short synthetic peptides used for epitope mapping. To identify the amino acids recognized by neutralizing and protective antibodies, we generated a recombinant vesicular stomatitis virus (VSV) containing the Ebola virus glycoprotein-encoding gene instead of the VSV G protein-encoding gene and used it to select escape variants by growing it in the presence of a MAb (133/3.16 or 226/8.1) that neutralizes the infectivity of the virus. All three variants selected by MAb 133/3.16 contained a single amino acid substitution at amino acid position 549 in the GP2 subunit. By contrast, MAb 226/8.1 selected three different variants containing substitutions at positions 134, 194, and 199 in the GP1 subunit, suggesting that this antibody recognized a conformational epitope. Passive transfer of each of these MAbs completely protected mice from a lethal Ebola virus infection. These data indicate that neutralizing antibody cocktails for passive prophylaxis and therapy of Ebola hemorrhagic fever can reduce the possibility of the emergence of antigenic variants in infected individuals. 相似文献