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91.
Escherichia coli alpha-hemolysin (HlyA) is a toxin protein that, in common with other members of the RTX family, contains a calcium-binding domain consisting of a number of Gly- and Asp-rich nonapeptides (17 in this case) repeated in tandem. Amino acid number 6 in these nonapeptides is almost invariably Asp, and occasionally Asn, but HlyA contains a His residue (number 859 in the chain) in position 6 of the last-but-one nonapeptide. HlyA mutants have been prepared, by site-directed mutagenesis, in which His-859 has been replaced by an Asn (H859N) or by Asp (H859D). HlyA exists in aqueous media in an aggregate-monomer equilibrium, but only the monomer containing bound Ca(2+) (HlyA.Ca) appears to be competent to achieve target membrane insertion and subsequent lysis. In mutant H859N, equilibrium appears to be shifted toward the aggregate, therefore the protein does not exchange Ca(2+) with the aqueous environment, no HlyA.Ca monomers are detected, and the protein lacks any membrane lytic activity. Mutant H859D in turn is almost indistinguishable from the wild-type regarding its calcium binding and membrane lytic activity, however, it differs significantly in its pH dependence. Wild-type HlyA activity decreases sigmoidally with pH, following rather closely the protonation curve of a His residue (apparent pK(a) approximately 6.5). With mutant H859D activity decreases almost linearly with pH and to a smaller extent. It can be concluded that His-859 plays a critical role in several aspects of HlyA activity, namely self-aggregation properties, calcium binding, hemolysis, and pH dependence. 相似文献
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96.
The chemical compositions of ground water and organic matter in sediments were investigated at a sandy shore of Tokyo Bay, Japan to determine the fate of ground water NO3
–. On the basis of Cl– distribution in ground water, the beach was classified into freshwater (FR)-, transition (TR)-, and seawater (SW)-zones from the land toward the shoreline. The NO3
– and N2O did not behave conservatively with respect to Cl– during subsurface mixing of freshwater and seawater, suggesting NO3
– consumption and N2O production in the TR-zone. Absence of beach vegetation indicated that NO3
– assimilation by higher plants was not as important as NO3
– sink. Low NH4
+ concentrations in ground water revealed little reduction of NO3
– to NH4
+. These facts implied that microbial denitrification and assimilation were the likely sinks for ground water NO3
–. The potential activity and number of denitrifiers in water-saturated sediment were highest in the low-chlorinity part of the TR-zone. The location of the highest potential denitrification activity (DN-zone) overlapped with that of the highest NO3
– concentration. The C/N ratio and carbon isotope ratio (13C) of organic matter in sediment (< 100 -m) varied from 12.0 to 22.5 and from –22.5 to –25.5, respectively. The 13C value was inversely related to the C/N ratio (r
2 = 0.968, n = 11), which was explained by the mixing of organic matters of terrestrial and marine origins. In the DN-zone, the fine sediments were rich in organic matters with high C/N ratios and low 13C values, implying that dissolved organic matters of terrestrial origin might have been immobilized under slightly saline conditions. A concurrent supply of NO3
– and organic matter to the TR-zone by ground water discharge probably generates favorable conditions for denitrifiers. Ground water NO3
– discharged to the beach is thus partially denitrified and fixed as microbial biomass before it enters the sea. Further studies are necessary to determine the relative contribution of these processes for NO3
– removal. 相似文献
97.
Lewin-Kowalik J Marcol W Kotulska-Wolwender K Larysz-Brysz M Swiech-Sabuda E Górka D Gołka B Małecka-Tendera E 《Acta physiologica Hungarica》2003,90(2):157-166
The effects of the repair of nerve gap injuries are still unsatisfactory, despite the great progress in microsurgery. Until now, there is no effective method to induce the regeneration of the transected peripheral nerve when its distal stump is missing. The aim of this work was to examine whether the implantation of dead-ended connective tissue chambers can promote the outgrowth of injured peripheral neurites. This method differs from all previous nerve guides because it totally eliminates the distal part of the nerve and restricts the influence of surrounding tissues. We have also tried to establish whether some neurotrophic factors can be applied by means of these chambers. The results of this work show that dead-ended autologous connective tissue chambers can be a useful tool in peripheral nerve injuries treatment, even when the distal part of the nerve is missing. 相似文献
98.
Quinapril inhibits progression of heart failure and fibrosis in rats with dilated cardiomyopathy after myocarditis 总被引:7,自引:0,他引:7
Juan W Nakazawa M Watanabe K Ma M Wahed MI Hasegawa G Naito M Yamamoto T Fuse K Kato K Kodama M Aizawa Y 《Molecular and cellular biochemistry》2003,251(1-2):77-82
The cardioprotective properties of quinapril, an angiotensin-converting enzyme inhibitor, were studied in a rat model of dilated cardiomyopathy. Twenty-eight days after immunization of pig cardiac myosin, four groups rats were given 0.2 mg/kg (Q0.2, n = 11), 2 mg/kg (Q2, n = 11) or 20 mg/kg (Q20, n = 11) of quinapril or vehicle (V, n = 15) orally once a day. After 1 month, left ventricular end-diastolic pressure (LVEDP), ±dP/dt, area of myocardial fibrosis, and myocardial mRNA expression of transforming growth factor (TGF)-1, collagen-III and fibronectin were measured. Four of 15 (27%) rats in V and two of 11 (18%) in Q0.2 died. None of the animals in Q2 or Q20 died. The LVEDP was higher and ±dP/dt was lower in V (14.1 ± 2.0 mmHg and +2409 ± 150/–2318 ± 235 mmHg/sec) than in age-matched normal rats (5.0 ± 0.6 mmHg and +6173 ± 191/–7120 ± 74 mmHg/sec; all p < 0.01). After quinapril treatment, LVEDP was decreased and ±dP/dt was increased in a dose-dependent manner (10.8 ± 1.8 mmHg and +3211 ± 307/–2928 ± 390 mmHg/sec in Q0.2, 9.4 ± 1.5 mmHg and +2871 ± 270/–2966 ± 366 mmHg/sec in Q2, and 6.6 ± 1.5 mmHg, and +3569 ± 169/–3960 ± 203 mmHg/sec in Q20). Increased expression levels of TGF-1, collagen-III and fibronectin mRNA in V were reduced in Q20. Quinapril improved survival rate and cardiac function in rats with dilated cardiomyopathy after myocarditis. Furthermore, myocardial fibrosis was regressed and myocardial structure returned to nearly normal in animals treated with quinapril. 相似文献
99.
Chong SH Joti Y Kidera A Go N Ostermann A Gassmann A Parak F 《European biophysics journal : EBJ》2001,30(5):319-329
The crystallographic normal mode refinements of myoglobin at a wide range of temperature from 40 K to 300 K were carried out to study the temperature dependence of the internal atomic fluctuations. The refinement method decomposes the mean square displacement from the average position, (deltar2), into the contributions from the internal degrees of freedom and those from the external degrees of freedom. The internal displacements show linear temperature dependence as (deltar2)=alphaT+beta, throughout the temperature range measured here, and exhibit no obvious change in the slope alpha at the dynamical transition temperature (Tc=ca. 180 K). The slope alpha is practically the same as the value predicted theoretically by normal mode analysis. Such linear dependence is considered to be due to the following reason. The crystallographic Debye-Waller factor represents the static distribution caused by convolution of temperature-dependent normal mode motions and a temperature-independent set of the conformational substates. In contrast, M?ssbauer absorption spectroscopy shows a clear increase in the gradient alpha at Tc. This difference from X-ray diffraction originates from the incoherent nature of the M?ssbauer effect together with its high-energy resolution, which yields the self-correlation, and the temporal behavior of individual Fe atoms in the myoglobin crystal. 相似文献
100.
The study was focused on the relationship of Fasciola hepatica-secreted proteinases and human IgG subclasses. Each IgG was incubated at different pH values and lengths of time with either the adult parasite excretion-secretion products or the purified cysteinyl proteinases cathepsin L1 and cathepsin L2. The Ig fragments produced were isolated and characterized by Western blot analysis, and the specific cleavage sites were determined by amino acid sequence analysis. Parasite excretion-secretion products and both cathepsins L produced similar degradation patterns and cleaved all human IgG subclasses at the hinge region, yielding at pH 7.3 and 37 degrees C Fab and Fc fragments in the case of IgG1 and IgG3 or Fab(2) and Fc in IgG2 and IgG4. While IgG1 and IgG3 were readily degraded by E/S products either in the presence or in the absence of reducing agents, IgG2 and IgG4 were resistant to proteolysis and were only digested in the presence of 0.1 M dithiothreitol. The cathepsins L needed the presence of dithiothreitol to digest IgG1, IgG2, and IgG4 whereas IgG3 was identically cleaved under both reducing and nonreducing conditions. The main cleavage sites produced by E/S products, CL1, or CL2 were located at the positions peptide bonds: His237-Thr238, Glu237-Cys239, Gly233-Asp234, and Ser241-Cys242 for gamma1, gamma2, gamma3, or gamma4, respectively. The enzymes gave additional splitting sites on the middle hinge of IgG3 to produce shorter Fc fragments and also produce Fd degradation of the IgG4. No cleavage specificity differences were found between CL1 and CL2, but they differed in the kinetics of IgG3 degradation. By lowering the pH, only the E/S products produced concomitant destruction of the Fc while preserving the Fab portion. Under all the conditions assayed the enzymes produced an Fc'-like fragment of 14-15 kDa corresponding to the whole CH3 domain of the immunoglobulin. Contrary to the extensive degradation produced by cathepsins on digested proteins, its actions on IgG subclasses were specific and restricted; thus, all the fragments produced could be potentially involved in the mechanisms used by the parasite to evade the host immune response. 相似文献