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1.
Transforming growth factor-β (TGF-β) signaling plays an important role in regulation of a wide variety of cellular processes. Canonical TGF-β signaling is mediated by Smads which were further regulated by several factors. We previously reported that E3 ubiquitin ligase CHIP (carboxyl terminus of Hsc70-interacting protein, also named Stub1) controlled the sensitivity of TGF-β signaling by modulating the basal level of Smad3 through ubiquitin-mediated degradation. Here, we present evidence that Hsp70 and Hsp90 regulate the complex formation of Smad3/CHIP. Furthermore, we observed that over-expressed Hsp70 or inhibition of Hsp90 by geldanamycin (GA) leads to facilitated CHIP-induced ubiquitination and degradation of Smad3, which finally enhances TGF-β signaling. In contrast, over-expressed Hsp90 antagonizes CHIP mediated Smad3 ubiquitination and degradation and desensitizes cells in response to TGF-β signaling. Taken together, our data reveal an opposite role of Hsp70 and Hsp90 in regulating TGF-β signaling by implicating CHIP-mediated Smad3 ubiquitination and degradation. This study provides a new insight into understanding the regulation of the TGF-β signaling by chaperones.  相似文献   
2.
Developing novel materials that tolerate thickness variations of the active layer is critical to further enhance the efficiency of polymer solar cells and enable large‐scale manufacturing. Presently, only a few polymers afford high efficiencies at active layer thickness exceeding 200 nm and molecular design guidelines for developing successful materials are lacking. It is thus highly desirable to identify structural factors that determine the performance of semiconducting conjugated polymers in thick‐film polymer solar cells. Here, it is demonstrated that thiophene rings, introduced in the backbone of alternating donor–acceptor type conjugated polymers, enhance the fill factor and overall efficiency for thick (>200 nm) solar cells. For a series of fluorinated semiconducting polymers derived from electron‐rich benzo[1,2‐b:4,5‐b′]dithiophene units and electron‐deficient 5,6‐difluorobenzo[2,1,3]thiazole units a steady increase of the fill factor and power conversion efficiency is found when introducing thiophene rings between the donor and acceptor units. The increased performance is a synergistic result of an enhanced hole mobility and a suppressed bimolecular charge recombination, which is attributed to more favorable polymer chain packing and finer phase separation.  相似文献   
3.

Objectives

To describe alcohol drinking patterns among participants in Katutura, Namibia, and to evaluate brief versions of the AUDIT against the full AUDIT to determine their effectiveness in detecting harmful drinking.

Methods

A cross-sectional survey was conducted in four constituencies and 639 participants, 18 years or older, completed a sociodemographic survey and the AUDIT. The effectiveness of the AUDIT-C (first three questions) and the AUDIT-3 (third question) was compared to the full AUDIT.

Results

Approximately 40% were identified as harmful, hazardous or likely dependent drinkers, with men having a higher likelihood than women (57.2% vs. 31.0%, p<.0001). Approximately 32% reported making and/or selling alcohol from home. The AUDIT-C performed best at a cutoff ≥ 3, better in men (sensitivity: 99.3%, specificity: 77.8%) than women (sensitivity: 91.7%, specificity: 77.4%). The AUDIT-3 performed poorly (maximum sensitivity: < 90%, maximum specificity: <51%). According to AUROC, the AUDIT-C performed better than the AUDIT-3.

Conclusions

A large proportion of participants met criteria for alcohol misuse, indicating a need for screening and referral for further evaluation and intervention. The AUDIT-C was almost as effective as the full AUDIT and may be easier to implement in clinical settings as a routine screening tool in resource-limited settings because of its brevity.  相似文献   
4.
Mechanical properties of cells have been recognized as a biomarker for cellular cytoskeletal organization. As chemical treatments lead to cell cytoskeletal rearrangements, thereby, modifications of cellular mechanical properties, investigating cellular mechanical property variations provides insightful knowledge to effects of chemical treatments on cancer cells. In this study, the effects of eight different anticancer drugs on the mechanical properties of human prostate cancer cell (PC-3) are investigated using a recently developed control-based nanoindentation measurement (CNM) protocol on atomic force microscope (AFM). The CNM protocol overcomes the limits of other existing methods to in-liquid nanoindentation measurement of live cells on AFM, particularly for measuring mechanical properties of live cells. The Young’s modulus of PC-3 cells treated by the eight drugs was measured by varying force loading rates over three orders of magnitude, and compared to the values of the control. The results showed that the Young’s modulus of the PC-3 cells increased substantially by the eight drugs tested, and became much more pronounced as the force load rate increased. Moreover, two distinct trends were clearly expressed, where under the treatment of Disulfiram, paclitaxel, and MK-2206, the exponent coefficient of the frequency- modulus function remained almost unchanged, while with Celebrex, BAY, Totamine, TPA, and Vaproic acid, the exponential rate was significantly increased.  相似文献   
5.
Few studies have compared the sensitivity of trauma questionnaires to disaster inventories for assessing the prevalence of exposure to natural disaster or associated risk for post-disaster psychopathology. The objective of this analysis was to compare reporting of disaster exposure on a trauma questionnaire (Brief Trauma Questionnaire [BTQ]) to an inventory of disaster experience. Between 2011 and 2014, a sample of 841 reproductive-aged southern Louisiana women were interviewed using the BTQ and completed a detailed inventory about exposure to hurricanes and flooding. Post-traumatic stress disorder (PTSD) symptomology was measured with the Post-Traumatic Stress Checklist, and depression with the Edinburgh Depression Scale. The single question addressing disaster exposure on the BTQ had a sensitivity of between 65% and 70% relative to the more detailed questions. Reporting disaster exposure on the BTQ was more likely for those who reported illness/injury due to a hurricane or flood (74%-77%) or danger (77-79%), compared to those who reported damage (69-71%) or evacuation (64-68%). Reporting disaster exposure on the BTQ was associated with depression (odds ratio [OR] 2.29, 95% confidence interval [CI] 1.43-3.68). A single question is unlikely to be useful for assessing the degree of exposure to disaster across a broad population, and varies in utility depending on the mental health outcome of interest: the single trauma question is useful for assessing depression risk.  相似文献   
6.
7.
8.

Purpose

Life cycle sustainability assessment is meaningful for the decision-makers/stakeholders to select the most sustainable option among multiple alternatives; however, there are usually various severe uncertainty problems in sustainability-oriented decision-making, i.e., the vagueness and ambiguity that existed in human judgments and the lack of information. This study aims at developing a novel life cycle multi-criteria sustainability assessment method for helping the decision-makers/stakeholders to determine the sustainability level of the industrial and energy systems. In part 1, an improved interval analytic hierarchy process (AHP) which allows multiple decision-makers/stakeholders to participate in the decision-making was developed to determine the weights of the criteria which were used in life cycle sustainability assessment.

Methods

It is usually difficult for the decision-makers/stakeholders to use the numbers from 1 to 9 and their reciprocals for determining the comparison matrix when using the traditional AHP method for weight calculation, because human judgments usually involve various uncertainties. In order to the overcome this weak point of the traditional AHP, an improved AHP, so-called interval AHP, in which, multiple decision-makers/stakeholders are allowed to participate in the decision-making and allowed to use interval numbers instead of crisp numbers to establish the comparison matrix for determining the weights of the criteria for life cycle sustainability assessment, has been developed.

Results and discussion

The proposed method was used to determine the weights of the four aspects for life cycle sustainability assessment including economic, safety, social, and environmental aspects. Five representative stakeholders were invited to participate in the decision-making. After Monte Carlo simulation, the final weights of the four aspects have been determined with the proposed interval AHP.

Conclusions and perspectives

An interval AHP method was developed for determining the weights of the criteria for life cycle sustainability assessment; the decision-makers are allowed to use interval numbers to establish the comparison matrix for weight calculation. The weighting coefficients determined by Monte Carlo method can accurately reflect the preferences and willingness of multi-actor comparing with the traditional AHP method. This paper merely presents a novel method to calculate the weights of the criteria for life cycle sustainability assessment, but the method for determining the sustainability performance has been presented in part 2.
  相似文献   
9.
10.
Despite the unfavorable band structure with twofold degeneracy at the valence band maximum, MgAgSb is still an excellent p‐type thermoelectric material for applications near room temperature. The intrinsically weak electron–phonon coupling, reflected by the low deformation potential Edef ≈ 6.3 eV, plays a crucial role in the relatively high power factor of MgAgSb. More importantly, Li is successfully doped into Mg site to tune the carrier concentration, leading to the resistivity reduction by a factor of 3 and a consequent increase in power factor by ≈30% at 300 K. Low lattice thermal conductivity can be simultaneously achieved by all‐scale hierarchical phonon scattering architecture including high density of dislocations and nanoscale stacking faults, nanoinclusions, and multiscale grain boundaries. Collectively, much higher average power factor ≈25 μW cm?1 K?2 with a high average ZT ≈ 1.1 from 300 to 548 K is achieved for 0.01 Li doping, which would result in a high output power density ≈1.56 W cm?2 and leg efficiency ≈9.2% by calculations assuming cold‐side temperature Tc = 323 K, hot‐side temperature Th = 548 K, and leg length = 2 mm.  相似文献   
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