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991.
Buckley GM Fosbeary R Fraser JL Gowers L Higueruelo AP James LA Jenkins K Mack SR Morgan T Parry DM Pitt WR Rausch O Richard MD Sabin V 《Bioorganic & medicinal chemistry letters》2008,18(12):3656-3660
Following the identification of a potent IRAK inhibitor through routine project cross screening, a novel class of IRAK-4 inhibitor was established. The SAR of imidazo[1,2-a]pyridino-pyridines and benzimidazolo-pyridines was explored. 相似文献
992.
Chong TT Cunnington R Williams MA Kanwisher N Mattingley JB 《Current biology : CB》2008,18(20):1576-1580
Mirror neurons, as originally described in the macaque, have two defining properties [1, 2]: They respond specifically to a particular action (e.g., bringing an object to the mouth), and they produce their action-specific responses independent of whether the monkey executes the action or passively observes a conspecific performing the same action. In humans, action observation and action execution engage a network of frontal, parietal, and temporal areas. However, it is unclear whether these responses reflect the activity of a single population that represents both observed and executed actions in a common neural code or the activity of distinct but overlapping populations of exclusively perceptual and motor neurons [3]. Here, we used fMRI adaptation to show that the right inferior parietal lobe (IPL) responds independently to specific actions regardless of whether they are observed or executed. Specifically, responses in the right IPL were attenuated when participants observed a recently executed action relative to one that had not previously been performed. This adaptation across action and perception demonstrates that the right IPL responds selectively to the motoric and perceptual representations of actions and is the first evidence for a neural response in humans that shows both defining properties of mirror neurons. 相似文献
993.
Plant lipid-transfer proteins (LTPs) are abundant, small, lipid binding proteins that are capable of exchanging lipids between membranes in vitro. Despite their name, a role in intracellular lipid transport is considered unlikely, based on their extracellular localization. A number of other biological roles, including antimicrobial defense, signaling, and cell wall loosening, have been proposed, but conclusive evidence is generally lacking, and these functions are not well correlated with in vitro activity or structure. A survey of sequenced plant genomes suggests that the two biochemically characterized families of LTPs are phylogenetically restricted to seed plants and are present as substantial gene families. This review aims to summarize the current understanding of LTP biochemistry, as well as the evidence supporting the proposed in vivo roles of these proteins within the emerging post-genomic framework. 相似文献
994.
Development and mapping of EST-derived simple sequence repeat markers for hexaploid wheat. 总被引:21,自引:0,他引:21
Ju-Kyung Yu Trevor M Dake Sukhwinder Singh David Benscher Wanlong Li Bikram Gill Mark E Sorrells 《Génome》2004,47(5):805-818
Expressed sequence tags (ESTs) are a valuable source of molecular markers. To enhance the resolution of an existing linkage map and to identify putative functional polymorphic gene loci in hexaploid wheat (Triticum aestivum L.), over 260,000 ESTs from 5 different grass species were analyzed and 5418 SSR-containing sequences were identified. Using sequence similarity analysis, 156 cross-species superclusters and 138 singletons were used to develop primer pairs, which were then tested on the genomic DNA of barley (Hordeum vulgare), maize (Zea mays), rice (Oryza sativa), and wheat. Three-hundred sixty-eight primer pairs produced PCR amplicons from at least one species and 227 primer pairs amplified DNA from two or more species. EST-SSR sequences containing dinucleotide motifs were significantly more polymorphic (74%) than those containing trinucleotides (56%), and polymorphism was similar for markers in both coding and 5' untranslated (UTR) regions. Out of 112 EST-SSR markers, 90 identified 149 loci that were integrated into a reference wheat genetic map. These loci were distributed on 19 of the 21 wheat chromosomes and were clustered in the distal chromosomal regions. Multiple-loci were detected by 39% of the primer pairs. Of the 90 mapped ESTs, putative functions for 22 were identified using BLASTX queries. In addition, 80 EST-SSR markers (104 loci) were located to chromosomes using nullisomic-tetrasomic lines. The enhanced map from this study provides a basis for comparative mapping using orthologous and PCR-based markers and for identification of expressed genes possibly affecting important traits in wheat. 相似文献
995.
Antarctic blue whales ( Balaenoptera musculus intermedia ) are the largest and formerly most abundant blue whale subspecies, but were hunted to near extinction last century. Estimated whaling mortality was unsustainable from 1928 to 1972 (except during 1942–1944), depleting them from 239,000 (95% interval 202,000–311,000) to a low of 360 (150–840) in 1973. Obtaining statistical evidence for subsequent increases has proved difficult due to their scarcity. We fitted Bayesian models to three sighting series (1968–2001), constraining maximum rates of increase to 12% per annum. These models indicated that Antarctic blue whales are increasing at a mean rate of 7.3% per annum (1.4%–11.6%). Informative priors based on blue whale biology (4.3%, SD = 1.9%) and a Bayesian hierarchical meta-analysis of increase rates in other blue whale populations (−3%, SD = 11.6%), suggest plausible increase rates are lower (although the latter has wide intervals), but a meta-analysis of other mysticetes obtains similar rates of increase (6.7%, SD = 4.0%). Possible biases affecting the input abundance estimates are discussed. Although Antarctic blue whales appear to have been increasing since Sovier illegal whaling ended in 1972, they still need to be protected-their estimated 1996 population size, 1,700 (860–2,900), was just 0.7% (0.3%–1.3%) of the pre-exploitation level. 相似文献
996.
Recent declines in many chinook salmon, Oncorhynchus tshawytscha, populations within the Columbia River watershed have prompted an examination of their reproductive biology. In a previous study many female fall chinook salmon collected in 1999 from the Hanford Reach of the Columbia River tested positive for a male-specific DNA marker (OtY1) found on the Y chromosome. The purpose of this study was to determine if females testing positive for the OtY1 marker could be found in other populations of fall chinook salmon from the Columbia River, and to assess the prevalence of OtY1 incidence in different female cohorts. Post-spawned male and female fall chinook salmon from three different naturally spawning populations (Hanford Reach, Yakima River and Ives Island) and one hatchery population (Priest Rapids Hatchery) on the Columbia River were tested in 2000 and 2001 for the OtY1 marker. Among naturally spawning populations, 57.4% of the females tested positive from the Hanford Reach, 33.3% tested positive from the Yakima River, and 32.5% tested positive from Ives Island. Of the Priest Rapids Hatchery fish, 62.5% of the females tested positive, and significant differences were detected between the 1995–1996 and 1997–1998 female cohorts from this population. No significant differences were detected between any of the female cohorts from the naturally spawning populations. All male chinook salmon samples, tested positive for OtY1. 相似文献
997.
998.
The secondary structure of the trimeric protein 4-chlorobenzoyl coenzyme A dehalogenase from Arthrobacter sp. strain TM-1, the second of three enzymes involved in the dechlorination of 4-chlorobenzoate to form 4-hydroxybenzoate, has
been examined. EmM for the enzyme was 12.59. Analysis by circular dichroism spectrometry in the far uv indicated that 4-chlorobenzoyl coenzyme
A dehalogenase was composed mostly of α-helix (56%) with lesser amounts of random coil (21%), β-turn (13%) and β-sheet (9%).
These data are in close agreement with a computational prediction of secondary structure from the primary amino acid sequence,
which indicated 55.8% α-helix, 33.7% random coil and 10.5% β-sheet; the enzyme is, therefore, similar to the 4-chlorobenzoyl
coenzyme A dehalogenase from Pseudomonas sp. CBS-3. The three-dimensional structure, including that of the presumed active site, predicted by computational analysis,
is also closely similar to that of the Pseudomonas dehalogenase. Study of the stability and physicochemical properties revealed that at room temperature, the enzyme was stable
for 24 h but was completely inactivated by heating to 60°C for 5 min; thereafter by cooling at 1°C min−1 to 45°C, 20.6% of the activity could be recovered. Mildly acidic (pH 5.2) or alkaline (pH 10.1) conditions caused complete
inactivation, but activity was fully recovered on returning the enzyme to pH 7.4. Circular dichroism studies also indicated
that secondary structure was little altered by heating to 60°C, or by changing the pH from 7.4 to 6.0 or 9.2. Complete, irreversible
destruction of, and maximal decrease in the fluorescence yield of the protein at 330–350 nm were brought about by 4.5 M urea
or 1.1 M guanidinium chloride. Evidence was obtained to support the hypothetical three-dimensional model, that residues W140
and W167 are buried in a non-polar environment, whereas W182 appears at or close to the surface of the protein. At least one
of the enzymes of the dehalogenase system (the combined 4-chlorobenzoate:CoA ligase, the dehalogenase and 4-hydroxybenzoyl
coenzyme A thioesterase) appears to be capable of association with the cell membrane.
相似文献
Anthony R. W. SmithEmail: |
999.
Catherine A Heyward Trevor R Pettitt Sophie E Leney Gavin I Welsh Jeremy M Tavaré Michael JO Wakelam 《BMC cell biology》2008,9(1):25
Background
Insulin stimulates glucose uptake by adipocytes through increasing translocation of the glucose transporter GLUT4 from an intracellular compartment to the plasma membrane. Fusion of GLUT4-containing vesicles at the cell surface is thought to involve phospholipase D activity, generating the signalling lipid phosphatidic acid, although the mechanism of action is not yet clear. 相似文献1000.