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981.
Powell HW Parker GJ Alexander DC Symms MR Boulby PA Barker GJ Thompson PJ Koepp MJ Duncan JS 《Journal of neurology, neurosurgery, and psychiatry》2008,79(3):327-330
Naming difficulties are a well recognised, but difficult to predict, complication of anterior temporal lobe resection (ATLR) for refractory epilepsy. We used MR tractography preoperatively to demonstrate the structural connectivity of language areas in patients undergoing dominant hemisphere ATLR. Greater lateralisation of tracts to the dominant hemisphere was associated with greater decline in naming function. We suggest that this method has the potential to predict language deficits in patients undergoing ATLR. 相似文献
982.
A graded forceps crush spinal cord injury model in mice 总被引:1,自引:0,他引:1
Plemel JR Duncan G Chen KW Shannon C Park S Sparling JS Tetzlaff W 《Journal of neurotrauma》2008,25(4):350-370
Given the rising availability and use of genetically modified animals in basic science research, it has become increasingly important to develop clinically relevant models for spinal cord injury (SCI) for use in mice. We developed a graded forceps crush model of SCI in mice that uses three different forceps with spacers of 0.25, 0.4, and 0.55 mm, to produce severe, moderate, and mild injuries, respectively. Briefly, each mouse was subjected to laminectomy of T5-T7, 15-second spinal cord crush using one of those forceps, behavioral assessments, and post-mortem neuroanatomical analyses. There were significant differences among the three injury severity groups on behavioral measures (Basso Mouse Score, footprint, and ladder analyses), demonstrating an increase in neurological deficits for groups with greater injury severity. Quantitative analysis of the lesion demonstrated that as injury severity increased, lesion size and GFAP negative area increased, and spared tissue, spinal cord cross-sectional area, spared grey matter and spared white matter decreased. These measures strongly correlated with the behavioral outcomes. Similar to other studies of SCI in mice, we report a dense laminin and fibronectin positive extracellular matrix in the lesion sites of injured mice, but unlike those previous studies, we also report the presence of numerous p75 positive Schwann cells in and around the lesion epicenter. These results provide evidence that the graded forceps crush model is an attractive alternative for the study of SCI and related therapeutic interventions. Because of its demonstrated consistency, ease of use, low cost, and clinical relevance, this graded forceps crush is an attractive alternative to the other mouse models of SCI currently available. 相似文献
983.
Homa Hosseinmardi Amir Ghasemian Aaron Clauset Markus Mobius David M. Rothschild Duncan J. Watts 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(32)
Although it is under-studied relative to other social media platforms, YouTube is arguably the largest and most engaging online media consumption platform in the world. Recently, YouTube’s scale has fueled concerns that YouTube users are being radicalized via a combination of biased recommendations and ostensibly apolitical “anti-woke” channels, both of which have been claimed to direct attention to radical political content. Here we test this hypothesis using a representative panel of more than 300,000 Americans and their individual-level browsing behavior, on and off YouTube, from January 2016 through December 2019. Using a labeled set of political news channels, we find that news consumption on YouTube is dominated by mainstream and largely centrist sources. Consumers of far-right content, while more engaged than average, represent a small and stable percentage of news consumers. However, consumption of “anti-woke” content, defined in terms of its opposition to progressive intellectual and political agendas, grew steadily in popularity and is correlated with consumption of far-right content off-platform. We find no evidence that engagement with far-right content is caused by YouTube recommendations systematically, nor do we find clear evidence that anti-woke channels serve as a gateway to the far right. Rather, consumption of political content on YouTube appears to reflect individual preferences that extend across the web as a whole.As affective political polarization rises in the United States (1) and trust in traditional sources of authority declines (2, 3), concerns have arisen regarding the presence, prevalence, and impact of false, hyperpartisan, or conspiratorial content on social media platforms. Most research on the potentially polarizing and misleading effects of social media has focused on Facebook and Twitter (4–12), reflecting a common view that these platforms are the most “news-oriented” social media platforms. However, roughly 23 million Americans rely on YouTube as a source of news (13, 14), a number comparable to the corresponding Twitter audience (13, 15), and it is growing in both size and engagement. YouTube news content spans the political spectrum, and includes content producers of all sizes. Recent work (16) has identified a large number of YouTube channels, mostly operated by individuals or small organizations, that promote a collection of “far-right” ideologies (e.g., white identitarian) and conspiracy theories (e.g., QAnon). The popularity of some of these channels, along with salient popular anecdotes, has prompted claims that YouTube’s recommendation engine systematically drives users to this content, and effectively radicalizes its users (17–20). For example, it has been reported that, starting from factual videos about the flu vaccine, the recommender system can lead users to antivaccination conspiracy videos (18).Recent qualitative work (21) has identified a separate collection of channels labeled variously as “reactionary,” “anti-woke” (AW), “anti-social justice warriors” (ASJW), “intellectual dark web” (IDW), or simply “antiestablishment.” Although these channels do not identify themselves as politically conservative, and often position themselves as nonideological or even liberal “free thinkers,” in practice, their positions are largely defined in opposition to progressive social justice movements, especially those concerning identity and race, as well as critiquing institutions such as academia and mainstream media for their “left-wing bias” (21, 22). Concurrently, “anti-woke” rhetoric has increasingly been adopted by mainstream Republican politicians (23), undermining claims that it is intrinsically apolitical. While anti-woke YouTube channels typically do not explicitly endorse far-right ideologies, some channel owners invite guests who are affiliated with the far right onto their shows and allow them to air their views relatively unchallenged, thereby effectively broadcasting and legitimizing far-right ideologies (21). If these channels act as a kind of gateway to the far right, they would constitute a related yet distinct radicalization mechanism from the recommendation system per se (17, 24). Based on these considerations, and recognizing that any label for this loose collection of channels is likely to be inaccurate for at least some members, we refer to them hereafter as anti-woke (AW).Although reports of various mechanisms driving people to politically radical content have received great attention, quantitative evidence to support them has proven elusive. On a platform with almost 2 billion users (25), it is possible to find examples of almost any type of behavior; hence anecdotes of radicalized individuals (17), however vivid, do not, on their own, indicate systematic problems. Thus, the observation that a particular mechanism (e.g., recommendation systems steering users to extreme content; far-right personalities appearing on anti-woke channels acting as gateways to the far right) might plausibly have a large and measurable effect on audiences does not substitute for measuring the effect. Finally, the few empirical studies (24, 26–29) that have examined the question of YouTube radicalization have reached conflicting conclusions, with some finding evidence for it (24, 26) and others finding the opposite (27, 28). These disagreements may arise from methodological differences that make results difficult to fairly compare—for example, ref. 28 examines potential biases in the recommender by simulating logged-out users, whereas ref. 24 reconstructs user histories from scraped comments. The disagreement may also reflect limitations in the available data, which is intrinsically ill suited to measuring either individual or aggregate consumption of different types of content over extended time intervals, such as user sessions or “lifetimes.” Absent such data for a large, representative sample of real YouTube users, it is difficult to evaluate how much far-right content is, in fact, being consumed (vs. produced), how it is changing over time, and to what extent it is being driven by YouTube’s own recommendations, spillovers from anti-woke channels, or other entry points.Here we investigate the consumption of radical political news content on YouTube using a unique dataset comprising a large () representative sample of the US population, and their online browsing histories, both on and off the YouTube platform, spanning 4 years from January 2016 to December 2019. To summarize, we present five main findings. 1) Consistent with previous estimates (30), we find that the total consumption of any news-related content on YouTube accounts for of overall consumption and is dominated by mainstream, and generally centrist or left-leaning, sources. 2) The consumption of far-right content is small in terms of both number of viewers and total watch time, where the former decreased slightly and the latter increased slightly over the observation period. 3) In contrast, the consumption of anti-woke content, while also small relative to mainstream or left-leaning content, grew in both numbers of users and total watch time. 4) The pathways by which users reach far-right videos are diverse, and only a fraction can plausibly be attributed to platform recommendations. Within sessions of consecutive video viewership, we find no trend toward more extreme content, either left or right, indicating that consumption of this content is determined more by user preferences than by recommendation. 5) Consumers of anti-woke, right, and far-right content also consume a meaningful amount of far-right content elsewhere online, indicating that, rather than the platform (either the recommendation engine or consumption of anti-woke content) pushing them toward far-right content, it is a complement to their larger news diet.These results indicate little evidence for the popular claim that YouTube drives users to consume more radical political content, either left or right. Instead, we find strong evidence that, while somewhat unique with its growing and dedicated anti-woke channels, YouTube should otherwise be viewed as part of a larger information ecosystem in which conspiracy theories, misinformation, and hyperpartisan content are widely available, easily discovered, and actively sought out (27, 31). 相似文献
984.
Innate immunity in the CNS depends primarily on the functions of glial cells, astrocytes and microglia, which are important for the early control of pathogen replication and direct the recruitment and activation of cells of the adaptive immune system required for pathogen clearance. Efficient immune responses are required for clearance of an invading pathogen, but dysregulation of a pro-inflammatory response in the CNS could lead to the development of autoimmunity. This review summarizes the activation of toll-like receptors (TLRs) expressed on glial cells and the functional outcome of these interactions for CNS health and disease which depends on a delicate balance of the protective and toxic effects of molecules induced in the CNS following TLR ligation. 相似文献
985.
Mohammed R Jimulia T Durve K Bansal M Green M Learmonth D 《Acta orthopaedica Belgica》2008,74(4):472-477
The results of a multi-surgeon, multi-implant series of patellofemoral joint arthroplasties performed over a ten year period are presented. All patellofemoral joint arthroplasties performed from 1997 to 2006 were retrospectively reviewed using case notes, radiographs and clinic appointments until their latest follow-up period. One hundred and one arthroplasties in 91 patients were followed up for an average period of 48 months (range 6-96 months). The average age was 57 years with female patients thrice as common as male patients. There were 5 (5%) complications with 1 deep infection and 4 stiff knees. Thirty five subsequent procedures were performed in 28 patients including arthroscopic debridement in 18, arthroscopic lateral retinacular release in 8, tibial tuberosity transfer in 3, manipulation for stiffness in 2, and revision to total knee arthroplasty in 4 patients (3 for progression of tibiofemoral osteoarthritis and 1 for infection). The necessity of further surgeries in one third of the study group suggests that close follow-up of these patients is needed to address any concerns that can be easily resolved. 相似文献
986.
987.
988.
Capell HA Madhok R Porter DR Munro RA McInnes IB Hunter JA Steven M Zoma A Morrison E Sambrook M Wui Poon F Hampson R McDonald F Tierney A Henderson N Ford I 《Annals of the rheumatic diseases》2007,66(2):235-241
BACKGROUND: Optimal use of disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis is vital if progression of disease is to be reduced. Methotrexate (MTX) and sulfasalazine (SASP) are widely used inexpensive DMARDs, recently often combined despite no firm evidence of benefit from previous studies. Aim: To establish whether a combination of SASP and MTX is superior to either drug alone in patients with rheumatoid arthritis with a suboptimal response to 6 months of SASP. METHODS: A randomised controlled study of step-up DMARD treatment in early rheumatoid arthritis. In phase I, 687 patients received SASP for 6 months. Those with a disease activity score (DAS) > or =2.4 were offered additional treatment in phase II (SASP alone, MTX alone or a combination of the two). The primary outcome measure was change in DAS. RESULTS: At 6 months, 191 (28%) patients had a DAS <2.4, 123 (18%) were eligible but did not wish to enter phase II, 130 (19%) stopped SASP because of reversible adverse events and 165 (24%) entered phase II. DAS at 18 months was significantly lower in those who received combination treatment compared with those who received either SASP or MTX: monotherapy arms did not differ. Improvement in European League Against Rheumatism and American College of Rheumatology 20, 50 and 70 scores favoured combination therapy. CONCLUSIONS: In this "true-to-life" study, an inexpensive combination of DMARDs proved more effective than monotherapy in patients with rheumatoid arthritis with a suboptimal response to SASP. There was no increase in toxicity. These results provide an evidence base for the use of this combination as a component of tight control strategies. 相似文献
989.
Loffler KA Biondi CA Gartside MG Serewko-Auret MM Duncan R Tonks ID Mould AW Waring P Muller HK Kay GF Hayward NK 《Oncogene》2007,26(27):4009-4017
To identify possible genetic interactions between the mechanisms of tumor suppression of menin and pRb, we intercrossed mice with targeted deletions of Men1 and Rb1, and compared tumor development in cohorts of animals carrying single or dual mutations of these tumor-suppressor genes. In mice lacking one copy of Men1, pancreatic islet and anterior pituitary adenomas are common. In animals lacking one copy of Rb1, intermediate pituitary and thyroid tumors occur at high frequency, with less frequent development of pancreatic islet hyperplasia and parathyroid lesions. In mice heterozygous for both Men1 and Rb1, pancreatic hyperplasia and tumors of the intermediate pituitary and thyroid occurred at high frequency. Serum measurements of calcium and glucose did not vary significantly between genotypic groups. Loss of heterozygosity at the Rb1 locus was common in pituitary and thyroid tumors, whereas loss of menin was observed in pancreatic and parathyroid lesions. The tumor spectrum in the double heterozygotes was a combination of pathologies seen in each of the individual heterozygotes, without decrease in age of onset, indicating independent, non-additive effects of the two mutations. Together with the lack of increased tumor spectrum, this suggests that menin and pRb function in a common pathway of tumor suppression. 相似文献
990.
Joerger M Huitema AD Richel DJ Dittrich C Pavlidis N Briasoulis E Vermorken JB Strocchi E Martoni A Sorio R Sleeboom HP Izquierdo MA Jodrell DI Féty R de Bruijn E Hempel G Karlsson M Tranchand B Schrijvers AH Twelves C Beijnen JH Schellens JH;EORTC-PAMM-NDDG 《Clinical pharmacokinetics》2007,46(12):1051-1068
AIMS: To investigate the population pharmacokinetics and pharmacodynamics of doxorubicin and cyclophosphamide in breast cancer patients. PATIENTS AND METHODS: Sixty-five female patients with early or advanced breast cancer received doxorubicin 60 mg/m(2) over 15 minutes followed by cyclophosphamide 600 mg/m(2) over 15 minutes. The plasma concentration-time data of both drugs were measured, and the relationship between drug pharmacokinetics and neutrophil counts was evaluated using nonlinear mixed-effect modelling. Relationships were explored between drug exposure (the area under the plasma concentration-time curve [AUC]), toxicity and tumour response. RESULTS: Fifty-nine patients had complete pharmacokinetic and toxicity data. In 50 patients with measurable disease, the objective response rate was 60%, with complete responses in 6% of patients. Both doxorubicin and cyclophosphamide pharmacokinetics were associated with neutrophil toxicity. Cyclophosphamide exposure (the AUC) was significantly higher in patients with at least stable disease (n = 44) than in patients with progressive disease (n = 6; 945 micromol . h/L [95% CI 889, 1001] vs 602 micromol . h/L [95% CI 379, 825], p = 0.0002). No such correlation was found for doxorubicin. Body surface area was positively correlated with doxorubicin clearance; AST and patient age were negatively correlated with doxorubicin clearance; creatinine clearance was positively correlated with doxorubicinol clearance; and occasional concurrent use of carbamazepine was positively correlated with cyclophosphamide clearance. CONCLUSIONS: The proposed inhibitory population pharmacokinetic-pharmacodynamic model adequately described individual neutrophil counts after administration of doxorubicin and cyclophosphamide. In this patient population, exposure to cyclophosphamide, as assessed by the AUC, might have been a predictor of the treatment response, whereas exposure to doxorubicin was not. A prospective study should validate cyclophosphamide exposure as a predictive marker for the treatment response and clinical outcome in this patient group. 相似文献