全文获取类型
收费全文 | 1399篇 |
免费 | 165篇 |
国内免费 | 1篇 |
出版年
2022年 | 14篇 |
2021年 | 15篇 |
2020年 | 12篇 |
2019年 | 9篇 |
2018年 | 18篇 |
2017年 | 14篇 |
2016年 | 20篇 |
2015年 | 40篇 |
2014年 | 42篇 |
2013年 | 76篇 |
2012年 | 62篇 |
2011年 | 67篇 |
2010年 | 38篇 |
2009年 | 50篇 |
2008年 | 74篇 |
2007年 | 63篇 |
2006年 | 63篇 |
2005年 | 56篇 |
2004年 | 62篇 |
2003年 | 71篇 |
2002年 | 62篇 |
2001年 | 34篇 |
2000年 | 33篇 |
1999年 | 39篇 |
1998年 | 18篇 |
1997年 | 15篇 |
1996年 | 20篇 |
1995年 | 18篇 |
1994年 | 15篇 |
1993年 | 10篇 |
1992年 | 44篇 |
1991年 | 51篇 |
1990年 | 46篇 |
1989年 | 35篇 |
1988年 | 27篇 |
1987年 | 18篇 |
1986年 | 16篇 |
1985年 | 26篇 |
1984年 | 12篇 |
1983年 | 14篇 |
1982年 | 11篇 |
1981年 | 9篇 |
1979年 | 8篇 |
1978年 | 11篇 |
1977年 | 9篇 |
1976年 | 10篇 |
1975年 | 8篇 |
1974年 | 13篇 |
1973年 | 11篇 |
1972年 | 9篇 |
排序方式: 共有1565条查询结果,搜索用时 15 毫秒
991.
992.
Müller W Groothuis TG Eising CM Daan S Dijkstra C 《Journal of evolutionary biology》2005,18(3):661-668
Female birds of several species have control over the production of daughters and sons. However, most studies failed to find a relationship between egg size and sex. This is intriguing as adjustment of egg size would constitute a powerful tool for the female to meet different resource demands of the sexes, particularly in size dimorphic species. Our results show that, within clutches of black-headed gulls (Larus ridibundus) the proportion of males was positively associated with egg mass. This applied for all three laying positions, independently of the absolute egg mass. There was a significant relationship between the distribution of the sexes over the laying sequence and the egg mass change. When egg mass decreased over the sequence, first-laid eggs were male biased and last-laid eggs female biased, and vice versa. The potential adaptive value of this allocation strategy is evaluated with regard to male sensitivity to egg quality and competitive differences between the sexes. 相似文献
993.
994.
Zafra O Ramírez S Castán P Moreno R Cava F Vallés C Caro E Berenguer J 《FEBS letters》2002,519(1-3):99-102
The pgr1 mutant of Arabidopsis thaliana carries a single point mutation (P194L) in the Rieske subunit of the cytochrome b6/f (cyt b6/f) complex and is characterised by a reduced electron transport activity at saturating light intensities in vivo. We have investigated the electron transport in this mutant under in vitro conditions. Measurements of P700 reduction kinetics and of photosynthetic electron transport rates indicated that electron transfer from cyt b6/f to photosystem I is not generally reduced in the mutant, but that the pH dependence of this reaction is altered. The data imply that the pH-dependent inactivation of electron transport through cyt b6/f is shifted by about 1 pH unit to more alkaline pH values in pgr1 thylakoids in comparison with wild-type thylakoids. This interpretation was confirmed by determination of the transmembrane deltapH at different stromal pH values showing that the lumen pH in pgr1 mutant plants cannot drop below pH 6 reflecting most likely a shift of the pK and/or the redox potential of the oxidised Rieske protein. 相似文献
995.
Signal-regulatory protein alpha-CD47 interactions are required for the transmigration of monocytes across cerebral endothelium 总被引:6,自引:0,他引:6
de Vries HE Hendriks JJ Honing H De Lavalette CR van der Pol SM Hooijberg E Dijkstra CD van den Berg TK 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(11):5832-5839
Monocyte infiltration into inflamed tissue requires their initial arrest onto the endothelial cells (ECs), followed by firm adhesion and subsequent transmigration. Although several pairs of adhesion molecules have been shown to play a role in the initial adhesion of monocytes to ECs, the mechanism of transendothelial migration is poorly defined. In this study, we have investigated the role of signal-regulatory protein (SIRP)alpha-CD47 interactions in monocyte transmigration across brain ECs. CD47 expression was observed in vivo on cerebral endothelium of both control animals and animals suffering from experimental allergic encephalomyelitis. To investigate whether SIRPalpha-CD47 interactions are instrumental in the trafficking of monocytes across cerebral EC monolayers, in vitro assays were conducted in which the migration of monocytes, but not adhesion, was found to be effectively diminished by blocking SIRPalpha and CD47 on monocytes and ECs, respectively. In this process, SIRPalpha was found to interact solely with its counterligand CD47 on ECs. Overexpression of the CD47 molecule on brain ECs significantly enhanced monocytic transmigration, but did not affect adhesion. SIRPalpha-CD47-mediated transendothelial migration involved Gi protein activity, a known signaling component of CD47. Finally, cross-linking of CD47 on brain ECs induced cytoskeletal reorganization of the endothelium, a process that was Gi protein independent. These data provide the first evidence that the interaction of CD47 with its monocytic counterligand SIRPalpha is of importance in the final step of monocyte trafficking into the brain, a critical event in the development of neuroinflammatory diseases. 相似文献
996.
Fusetti F von Moeller H Houston D Rozeboom HJ Dijkstra BW Boot RG Aerts JM van Aalten DM 《The Journal of biological chemistry》2002,277(28):25537-25544
Chitin hydrolases have been identified in a variety of organisms ranging from bacteria to eukaryotes. They have been proposed to be possible targets for the design of novel chemotherapeutics against human pathogens such as fungi and protozoan parasites as mammals were not thought to possess chitin-processing enzymes. Recently, a human chitotriosidase was described as a marker for Gaucher disease with plasma levels of the enzyme elevated up to 2 orders of magnitude. The chitotriosidase was shown to be active against colloidal chitin and is inhibited by the family 18 chitinase inhibitor allosamidin. Here, the crystal structure of the human chitotriosidase and complexes with a chitooligosaccharide and allosamidin are described. The structures reveal an elongated active site cleft, compatible with the binding of long chitin polymers, and explain the inactivation of the enzyme through an inherited genetic deficiency. Comparison with YM1 and HCgp-39 shows how the chitinase has evolved into these mammalian lectins by the mutation of key residues in the active site, tuning the substrate binding specificity. The soaking experiments with allosamidin and chitooligosaccharides give insight into ligand binding properties and allow the evaluation of differential binding and design of species-selective chitinase inhibitors. 相似文献
997.
On the basis of crystal structures of the pyrroloquinoline quinone (PQQ) dependent enzymes methanol dehydrogenase (MDH) and soluble glucose dehydrogenase (s-GDH), different catalytic mechanisms have been proposed. However, several lines of biochemical and kinetic evidence are strikingly similar for both enzymes. To resolve this discrepancy, we have compared the structures of these enzymes in complex with their natural substrates in an attempt to bring them in line with a single reaction mechanism. In both proteins, PQQ is located in the center of the molecule near the axis of pseudo-symmetry. In spite of the absence of significant sequence homology, the overall binding of PQQ in the respective active sites is similar. Hydrogen bonding interactions are made with polar protein side chains in the plane of the cofactor, whereas hydrophobic stacking interactions are important below and above PQQ. One Arg side chain and one calcium ion are ligated to the ortho-quinone group of PQQ in an identical fashion in either active site, in agreement with their proposed catalytic function of polarizing the PQQ C5-O5 bond. The substrates are bound in a similar position above PQQ and within hydrogen bond distance of the putative general bases Asp297 (MDH) and His144 (s-GDH). On the basis of these similarities, we propose that MDH and s-GDH react with their substrates through an identical mechanism, comprising general base-catalyzed hydride transfer from the substrate to PQQ and subsequent tautomerization of the PQQ intermediate to reduced PQQ. 相似文献
998.
Secondary structure alone is generally not statistically significant for the detection of noncoding RNAs 总被引:14,自引:0,他引:14
MOTIVATION: Several results in the literature suggest that biologically interesting RNAs have secondary structures that are more stable than expected by chance. Based on these observations, we developed a scanning algorithm for detecting noncoding RNA genes in genome sequences, using a fully probabilistic version of the Zuker minimum-energy folding algorithm. RESULTS: Preliminary results were encouraging, but certain anomalies led us to do a carefully controlled investigation of this class of methods. Ultimately, our results argue that for the probabilistic model there is indeed a statistical effect, but it comes mostly from local base-composition bias and not from RNA secondary structure. For the thermodynamic implementation (which evaluates statistical significance by doing Monte Carlo shuffling in fixed-length sequence windows, thus eliminating the base-composition effect) the signals for noncoding RNAs are still usually indistinguishable from noise, especially when certain statistical artifacts resulting from local base-composition inhomogeneity are taken into account. We conclude that although a distinct, stable secondary structure is undoubtedly important in most noncoding RNAs, the stability of most noncoding RNA secondary structures is not sufficiently different from the predicted stability of a random sequence to be useful as a general genefinding approach. 相似文献
999.
Willatt L Cox J Barber J Cabanas ED Collins A Donnai D FitzPatrick DR Maher E Martin H Parnau J Pindar L Ramsay J Shaw-Smith C Sistermans EA Tettenborn M Trump D de Vries BB Walker K Raymond FL 《American journal of human genetics》2005,77(1):154-160
We report the identification of six patients with 3q29 microdeletion syndrome. The clinical phenotype is variable despite an almost identical deletion size. The phenotype includes mild-to-moderate mental retardation, with only slightly dysmorphic facial features that are similar in most patients: a long and narrow face, short philtrum, and high nasal bridge. Autism, gait ataxia, chest-wall deformity, and long and tapering fingers were noted in at least two of six patients. Additional features--including microcephaly, cleft lip and palate, horseshoe kidney and hypospadias, ligamentous laxity, recurrent middle ear infections, and abnormal pigmentation--were observed, but each feature was only found once, in a single patient. The microdeletion is approximately 1.5 Mb in length, with molecular boundaries mapping within the same or adjacent bacterial artificial chromosome (BAC) clones at either end of the deletion in all patients. The deletion encompasses 22 genes, including PAK2 and DLG1, which are autosomal homologues of two known X-linked mental retardation genes, PAK3 and DLG3. The presence of two nearly identical low-copy repeat sequences in BAC clones on each side of the deletion breakpoint suggests that nonallelic homologous recombination is the likely mechanism of disease causation in this syndrome. 相似文献
1000.
Kempiak SJ Yamaguchi H Sarmiento C Sidani M Ghosh M Eddy RJ Desmarais V Way M Condeelis J Segall JE 《The Journal of biological chemistry》2005,280(7):5836-5842
Activation of the epidermal growth factor (EGF) receptor can stimulate actin polymerization via the Arp2/3 complex using a number of signaling pathways, and specific stimulation conditions may control which pathways are activated. We have previously shown that localized stimulation of EGF receptor with EGF bound to beads results in localized actin polymerization and protrusion. Here we show that the actin polymerization is dependent upon activation of the Arp2/3 complex by neural Wiskott-Aldrich Syndrome protein (N-WASP) via Grb2 and Nck2. Suppression of Grb2 or Nck2 results in loss of localization of N-WASP at the activation site and reduced actin polymerization. Although cortactin has been found to synergize with N-WASP for Arp2/3-dependent actin polymerization in vitro, we find that cortactin can restrict N-WASP localization around EGF-bead-induced protrusions. In addition, cortactin-deficient cells have increased lamellipod dynamics but show reduced net translocation, suggesting that cortactin can contribute to cell polarity by controlling the extent of Arp2/3 activation by WASP family members and the stability of the F-actin network. 相似文献