全文获取类型
收费全文 | 3626篇 |
免费 | 263篇 |
国内免费 | 5篇 |
专业分类
3894篇 |
出版年
2023年 | 23篇 |
2022年 | 32篇 |
2021年 | 71篇 |
2020年 | 47篇 |
2019年 | 92篇 |
2018年 | 87篇 |
2017年 | 59篇 |
2016年 | 127篇 |
2015年 | 188篇 |
2014年 | 205篇 |
2013年 | 263篇 |
2012年 | 309篇 |
2011年 | 264篇 |
2010年 | 141篇 |
2009年 | 124篇 |
2008年 | 207篇 |
2007年 | 230篇 |
2006年 | 186篇 |
2005年 | 176篇 |
2004年 | 144篇 |
2003年 | 133篇 |
2002年 | 131篇 |
2001年 | 50篇 |
2000年 | 33篇 |
1999年 | 44篇 |
1998年 | 39篇 |
1997年 | 31篇 |
1996年 | 44篇 |
1995年 | 37篇 |
1994年 | 23篇 |
1993年 | 35篇 |
1992年 | 30篇 |
1991年 | 18篇 |
1990年 | 13篇 |
1989年 | 28篇 |
1988年 | 19篇 |
1987年 | 12篇 |
1986年 | 9篇 |
1985年 | 9篇 |
1984年 | 23篇 |
1983年 | 12篇 |
1982年 | 17篇 |
1981年 | 10篇 |
1980年 | 7篇 |
1979年 | 13篇 |
1978年 | 8篇 |
1977年 | 6篇 |
1974年 | 15篇 |
1971年 | 6篇 |
1964年 | 6篇 |
排序方式: 共有3894条查询结果,搜索用时 15 毫秒
991.
992.
993.
A discrete repeated sequence defines a tubulin binding domain on microtubule-associated protein tau 总被引:1,自引:0,他引:1
R B Maccioni J C Vera J Dominguez J Avila 《Archives of biochemistry and biophysics》1989,275(2):568-579
The protein domain responsible for the interaction of tau with tubulin has been identified. Biophysical studies indicated that the synthetic peptide Val187-Gly204 (VRSKIG-STENLKHQPGGG) from the repetitive sequence on tau binds to two sites on the tubulin heterodimer and to one site on each of the microtubule-associated protein-interacting C-terminal tubulin peptides alpha(430-441) and beta(422-434). The binding data showed a relatively stronger interaction of Val187-Gly204 with beta(422-434) as compared to that with alpha(430-441). The interaction of this tau peptide with either alpha or beta tubulin peptides appears to be associated with conformational changes in both the tau and the tubulin peptides. The beta tubulin peptide also appears to induce a structural change of tau fragment Val218-Gly235. Interestingly, tau peptides Val187-Gly204 and Val218-Gly235 induced tubulin self-assembly in a cold-reversible fashion, and incorporated into the assembled polymers. The specificity of the interaction of the tau peptide was supported by the competition of tau protein for the interaction with the tubulin polymer. In addition, the tau peptide appears to contain the principal antigenic determinant(s) recognized by anti-idiotypic antibodies that react with the tubulin binding domains on microtubule-associated proteins. The present findings together with the demonstration of the presence of multiple sites for the binding of the alpha(430-441) and beta(422-434) tubulin fragments to tau, and the existence of repetitive sequences on tau, strongly support the hypothesis that the region of tau defined by the repetitive sequences is involved in its interaction with tubulin. 相似文献
994.
Hong-Wen Deng Vera Haynatzka Ken Spitze Gleb Haynatzki 《Evolution; international journal of organic evolution》1999,53(5):1592-1599
There is much interest in measuring selection, quantifying evolutionary constraints, and predicting evolutionary trajectories in natural populations. For these studies, genetic (co)variances among fitness traits play a central role. We explore the conditions that determine the sign of genetic covariances and demonstrate a critical role of selection in shaping genetic covariances. In addition, we show that genetic covariance matrices rather than genetic correlation matrices should be characterized and studied in order to infer genetic basis of population differentiation and/or to predict evolutionary trajectories. 相似文献
995.
Vera Lucia Lanchote Evandro Jos Cesarino Vernica Jorge Santos Yussif Mere Silvia Regina Cavani Jorge Santos 《Chirality》1999,11(1):29-32
The phenomenon of enantioselectivity in the metabolism of mexiletine (MEX) conjugation was investigated in eight female patients with the arrhythmic form of chronic Chagas' heart disease treated with racemic mexiletine hydrochloride (two 100 mg capsules every 8 hr). Blood samples were collected up to 24 hr after the administration of the morning dose, with discontinuation of the subsequent doses during the study period. Plasma concentrations of N‐hydroxymexiletine glucuronide were calculated as the difference between the concentrations of unchanged and total (unchanged + conjugated) MEX enantiomers. Total plasma MEX concentrations were analyzed by HPLC after enzymatic hydrolysis with β‐glucuronidase, the formation of diastereomeric derivatives with the chiral reagent N‐acetyl‐l ‐cysteine/o‐phthalaldehyde, and fluorescence detection. The differences in the pharmacokinetic parameters of the enantiomers were evaluated by the paired t‐test. The plasma concentrations of the (+)‐(S)‐MEX did not differ before and after enzymatic hydrolysis. The pharmacokinetic parameters calculated for (−)‐(R)‐N‐hydroxymexiletine glucuronide are presented as means (95% confidence interval): maximum plasma concentration Cmax = 194.0 ng · ml−1 (154.3–233.7), time to maximum plasma concentration tmax = 1.4 hr (0.3–2.5), area under the plasma concentration versus time curve AUC0–24 = 2099.2 ng · h · ml−1 (1585.6–2612.6), elimination half‐life t1/2β = 12.8 hr (9.9–15.6) and extent of conjugation of 31.6% (24.3–38.9%). The present data indicate stereospecific conjugation of (−)‐(R)‐N‐hydroxymexiletine in the female patients with the arrhythmic form of Chagas' heart disease. Chirality 11:29–32, 1999. © 1999 Wiley‐Liss, Inc. 相似文献
996.
997.
Volkov RA Komarova NY Panchuk II Hemleben V 《Molecular phylogenetics and evolution》2003,29(2):187-202
The 5(') external transcribed spacer (ETS) region of ribosomal DNA of 30 species of Solanum sect. Petota and the European Solanum dulcamara were compared. Two structural elements can be distinguished in the ETS: (i). a variable region (VR), demonstrating significant structural rearrangements and (ii). a conservative region (CR), evolving mainly by base substitutions. In VR, a conservative element (CE) with similarity to the ETS of distantly related Nicotiana is present. The ancestral organization of ETS (variant A) was found for non-tuber-bearing species of ser. Etuberosa, tuber-bearing wild potatoes of Central American ser. Bulbocastana, Pinnatisecta, and Polyadenia and S. dulcamara. Duplication of CE took place in the ETS of species from ser. Commersoniana and Circaeifolia (variant B). South American diploids and Mexican polyploids from superser. Rotata also possess two CE, and additionally two duplications around CE1 are present in VR (variant C). Three major lineages could be distinguished: non-tuber-bearing species of ser. Etuberosa, tuber-bearing Central American diploids and all South American species radiated from a common ancestor at early stages of evolution, indicating a South American origin of the tuber-bearing species. Later, Central and South American diploids evolved further as independent lineages. South American species form a monophyletic group composed of series with both stellata and rotata flower morphology. Solanum commersonii represents a sister taxon for all rotata species, whereas ser. Circaeifolia diverged earlier. Two main groups, C1 and C2, may be distinguished for species possessing ETS variant C. C1 contains ser. Megistacroloba, Conicibaccata, Maglia, and Acaulia, whereas all diploids of ser. Tuberosa are combined into C2. A closer relationship of Solanum chacoense (ser. Yungasensa) to the C2 group was found. The origin of polyploid species Solanum maglia, Solanum acaule, Solanum tuberosum, Solanum iopetalum, and Solanum demissum is discussed. 相似文献
998.
Systemic deletion of the myelin-associated outgrowth inhibitor Nogo-A improves regenerative and plastic responses after spinal cord injury 总被引:42,自引:0,他引:42
Simonen M Pedersen V Weinmann O Schnell L Buss A Ledermann B Christ F Sansig G van der Putten H Schwab ME 《Neuron》2003,38(2):201-211
To investigate the role of the myelin-associated protein Nogo-A on axon sprouting and regeneration in the adult central nervous system (CNS), we generated Nogo-A-deficient mice. Nogo-A knockout (KO) mice were viable, fertile, and not obviously afflicted by major developmental or neurological disturbances. The shorter splice form Nogo-B was strongly upregulated in the CNS. The inhibitory effect of spinal cord extract for growing neurites was decreased in the KO mice. Two weeks following adult dorsal hemisection of the thoracic spinal cord, Nogo-A KO mice displayed more corticospinal tract (CST) fibers growing toward and into the lesion compared to their wild-type littermates. CST fibers caudal to the lesion-regenerating and/or sprouting from spared intact fibers-were also found to be more frequent in Nogo-A-deficient animals. 相似文献
999.
Inducible aluminum resistance of Acidiphilium cryptum and aluminum tolerance of other acidophilic bacteria 总被引:1,自引:0,他引:1
Fischer J Quentmeier A Gansel S Sabados V Friedrich CG 《Archives of microbiology》2002,178(6):554-558
Aluminum ions are highly soluble in acidic environments. Toxicity of aluminum ions for heterotrophic, facultatively and obligately chemolithoautotrophic acidophilic bacteria was examined. Acidiphilium cryptum grew in glucose-mineral medium, pH 3, containing 300 mM aluminum sulfate [Al(2)(SO(4))(3)] after a lag phase of about 120 h with a doubling time of 7.6 h, as compared to 5.2 h of growth without aluminum. Precultivation with 1 mM Al(2)(SO(4))(3) and transfer to a medium with 300 mM Al(2)(SO(4))(3) reduced the lag phase from 120 to 60 h, and immediate growth was observed when A. cryptum was precultivated with 50 mM Al(2)(SO(4))(3), suggesting an aluminum-induced resistance. Aluminum resistance was not induced by Fe(3+) ions and divalent cations. Upon exposure of A. cryptum to 300 mM Al(2)(SO(4))(3), the protein profile changed significantly as determined by SDS-PAGE. When other acidophiles were cultivated with 50-200 mM aluminum sulfate, no lag phase was observed while the growth rates and the cellular yields were significantly reduced. This growth response was observed with Acidobacterium capsulatum, Acidiphilium acidophilum, Acidithiobacillus ferrooxidans, and Acidithiobacillus thiooxidans. Precultivation of these strains with aluminum ions did not alter the growth response caused by aluminum. The content of A. cryptum cultivated with 300 mM Al(2)(SO(4))(3)was 0.44 microg Al/mg cell dry weight, while that of the other strains cultivated with 50 mM Al(2)(SO(4))(3) ranged from 0.30 to 3.47 microg Al/mg cell dry weight. 相似文献
1000.
Rubin BB Downey GP Koh A Degousee N Ghomashchi F Nallan L Stefanski E Harkin DW Sun C Smart BP Lindsay TF Cherepanov V Vachon E Kelvin D Sadilek M Brown GE Yaffe MB Plumb J Grinstein S Glogauer M Gelb MH 《The Journal of biological chemistry》2005,280(9):7519-7529
The role of a cytosolic phospholipase A(2)-alpha (cPLA(2)-alpha) in neutrophil arachidonic acid release, platelet-activating factor (PAF) biosynthesis, NADPH oxidase activation, and bacterial killing in vitro, and the innate immune response to bacterial infection in vivo was examined. cPLA(2)-alpha activity was blocked with the specific cPLA(2)-alpha inhibitor, Pyrrolidine-1 (human cells), or by cPLA(2) -alpha gene disruption (mice). cPLA(2)-alpha inhibition or gene disruption led to complete suppression of neutrophil arachidonate release and PAF biosynthesis but had no effect on neutrophil NADPH oxidase activation, FcgammaII/III or CD11b surface expression, primary or secondary granule secretion, or phagocytosis of Escherichia coli in vitro. In contrast, cPLA(2)-alpha inhibition or gene disruption diminished neutrophil-mediated E. coli killing in vitro, which was partially rescued by exogenous arachidonic acid or PAF but not leukotriene B(4). Following intratracheal inoculation with live E. coli in vivo, pulmonary PAF biosynthesis, inflammatory cell infiltration, and clearance of E. coli were attenuated in cPLA(2)-alpha(-/-) mice compared with wild type littermates. These studies identify a novel role for cPLA(2)-alpha in the regulation of neutrophil-mediated bacterial killing and the innate immune response to bacterial infection. 相似文献